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65Drew A. Torigian, MD, MA, and Charles T. Lau, MD

Solitary and Multiple pulMonary noduleS

1. What is a solitary pulmonary nodule (SPN)?SPN is a solitary focal lesion in the lung that measures 3 cm or less. A solitary focal lesion that is greater than 3 cm is considered to be a mass, and most masses are malignant. Approximately 150,000 SPNs are detected annually in the United States, often incidentally on imaging. About 60% are benign, but 40% can be malignant. The goal of radiologic evaluation of SPN is to differentiate noninvasively whether it is benign or malignant as accurately as possible. SPN is the initial radiographic finding in 30% of patients with lung cancer, and the prognosis depends partly on the stage at presentation.

2. List some causes of pulmonary nodules.Primary lung carcinoma is the most common cause of SPN; pulmonary granuloma is the second most common overall cause; and pulmonary hamartoma the third most common cause. Table 65-1 provides a more complete list. Many other entities can cause SPNs or multiple pulmonary nodules, including tumors (e.g., metastatic disease), infections, vasculitis, and inflammatory diseases (e.g., sarcoidosis, rheumatoid arthritis, or inhalational lung disease). Be careful about a “confluence of shadows” or overlap of normal vascular and osseous structures that appears to represent a nodule. Nipple shadows can also appear as nodules, but are usually seen at a similar level bilaterally.

3. What is the general approach to the evaluation of SPN?The initial step is to determine whether a visualized “nodule” on chest radiography is truly a pulmonary nodule or a pseudolesion that mimics a nodule (some of the causes of a pseudolesion are listed in Table 65-1). If a “nodule” is actually a pseudolesion associated with bone, such as a rib fracture, it would have the same anatomic relationship to its bone of origin on radiographs with multiple views, whereas a true pulmonary nodule that overlaps with osseous structures on one view would appear to move apart from these osseous structures on other views. Radiopaque nipple markers can be used to distinguish pseudolesions that are actually nipples from true pulmonary nodules. When a true SPN has been confirmed, a more detailed investigation begins.

4. What further diagnostic steps may be implemented in the work-up of indeterminate pulmonary nodules?Thin-section unenhanced computed tomography (CT), CT nodule densitometry, fluorodeoxyglucose (FDG) positron emission tomography (PET), short-term follow-up chest radiography or CT, and tissue sampling are some of the options available for the work-up of indeterminate pulmonary nodules. The choice is based on several factors, including the pretest probability of malignancy, the morphologic features of the nodules, and the patient’s clinical history and current status. Thin-section unenhanced CT is useful for the identification of fat or certain patterns of calcification within a nodule that indicate benignancy.

5. What are some potential blind spots on chest radiography and CT when trying to detect pulmonary nodules?• On chest radiography, potential blind spots include the lung apices where the clavicles and ribs overlap, the hila and

retrocardiac region where superimposed cardiovascular structures are located, and within the lung bases below the level of the anterior portions of the hemidiaphragms where abdominal soft tissue overlaps.

• On CT, potential blind spots include the central portions of the lungs (e.g., the hilar regions and the azygoesophageal recess) and the endoluminal portions of the trachea and bronchi.

6. List some morphologic imaging features of nodules assessed on chest radiography and CT.• Shape• Size/volume and change over time• Margins• Internal architecture• Presence of fat• Presence and pattern of calcification

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452 Solitary and Multiple pulMonary noduleS

Table 65-1. Differential Diagnosis of Solitary Pulmonary Nodule (SPN)NeoplasiaPrimary lung carcinoma (No. 1 cause of SPN)

Metastasis

Lymphoma/post-transplant lymphoproliferative disorder

Carcinoid tumor

Primary lung sarcoma

Hamartoma (No. 3 cause of SPN, No. 2 cause of benign SPN)InfectionGranuloma (No. 2 cause of SPN, No. 1 cause of benign SPN)

Bacterial

Viral

Fungal

Mycobacterial

Parasitic

Septic emboli (often multiple, peripheral, and cavitary)VascularPulmonary infarction (often peripheral and wedge-shaped, associated with pulmonary embolism)

Vasculitis

Arteriovenous malformation

Pulmonary venous varix (tubular and avidly enhancing on CT)

Pulmonary artery aneurysmInflammatorySarcoidosis

Inhalational lung disease

Hypersensitivity pneumonitis

Organizing pneumonia

Bronchiolitis

Langerhans cell histiocytosis (associated with upper lobe predominant cystic interstitial lung disease in smokers)

Rheumatoid (necrobiotic) nodule

Inflammatory pseudotumor

Congenital

Intrapulmonary lymph node

Pulmonary sequestration (solid or cystic opacity most often in lower lobes)

Bronchial atresiaTraumaticRadiation therapy (typically has linear margins and known history of prior radiation therapy)

Pulmonary contusion (associated with traumatic injury to chest)PseudonodulesRounded atelectasis (“folded lung,” typically subpleural opacity associated with pleural thickening or effusion

and “comet-tail sign” of swirling bronchovascular structures central to opacity)

Pulmonary scarring

Mucoid impaction

Fluid in interlobar fissure (often lenticular in shape on lateral chest radiograph in the location of a fissure)

Healing rib fracture

Bone island

Spinal osteophyte

Skin lesion

Nipple shadow

Pleural lesion

Mediastinal lesion

Overlap of vascular and osseous structures

Solitary and Multiple pulMonary noduleS 453thoracic radiology

Figure 65-1. Pulmonary hamartoma on CT. Note smoothly marginated round nodule (arrow) that contains low-attenuation fat pathognomonic for hamartoma.

7. Describe morphologic imaging findings that are suggestive of a benign SPN.Small size and smooth, well-defined margins suggest a benign SPN, although 15% and 40% of malignant nodules are less than 1 cm and 2 cm in diameter, and 20% of malignant nodules have well-defined margins. Intranodular fat is a reliable indicator of a hamartoma, which is a benign lesion (Fig. 65-1). Central, diffuse solid, laminated, and “popcorn-like” patterns of nodule calcification are indicative of benignancy, with the first three typically seen in calcified granulomas and the last in a pulmonary hamartoma (Fig. 65-2). Other patterns of calcification are nonspecific, and 15% of lung carcinomas may contain amorphous, stippled, or punctate and eccentric calcification. Avidly enhancing serpentine or tubular feeding arteries and an early draining vein associated with an enhancing nidus are pathognomonic of an arteriovenous malformation (Fig. 65-3). Small satellite nodules around the periphery of a smooth dominant nodule strongly suggest a granulomatous infection. Ground-glass opacity surrounding a nodule (“CT halo” sign) is highly suggestive of angioinvasive opportunistic infection,
such as by aspergillosis, particularly in the setting of neutropenia (Fig. 65-4). A three-dimensional ratio of the nodule’s largest axial diameter to the largest craniocaudal diameter greater than 1.78:1 (i.e., a flattened configuration) is highly suggestive of benignancy. A peripheral rim of enhancement or the “enhancing rim” sign of a nodule also suggests a benign SPN.
8. Describe morphologic imaging findings that are suggestive of a malignant SPN.Size greater than 2 cm suggests malignancy. Lobulated or spiculated margins with distortion of adjacent vessels are typically associated with malignancy, although a lobulated or spiculated margin is seen in 25% and 10% of benign nodules. The “corona radiata” sign consists of very fine linear strands extending outward from a nodule and is strongly suggestive of malignancy. Partially solid nodules (i.e., nodules composed of ground-glass and solid components) tend to be malignant and are most often due to bronchioloalveolar cell carcinoma (BAC) or adenocarcinoma with BAC features. Internal inhomogeneity, particularly from cystic/bubbly lucencies or pseudocavitation, strongly suggests malignancy, most often from BAC. Cavitary nodules with maximal wall thickness greater than 15 mm and wall irregularity tend to be malignant, whereas nodules with wall thickness 4 mm or less tend to be benign.

9. How does measurement of the doubling time of nodules aid in the determination of a benign SPN?Doubling time, the time required for a nodule to double in volume (equivalent to an increase of about 26% in diameter), for most malignant nodules is 1 to 15 months. Nodules that double in volume more rapidly or more slowly than this are typically benign. Generally, lack of growth of a nodule over a 2-year period is strongly suggestive of benignancy, although some malignant nodules, such as nodules secondary to BAC, bronchial carcinoid, or some pulmonary metastases, may take longer to grow. Follow-up CT scans for indeterminate pulmonary nodules generally are performed at 3 to 12 months after the initial CT scan to assess for interval growth depending on the size and appearance of the nodule and the presence of risk factors for malignancy, such as a patient history of tobacco use.

Central Diffuse solid Laminated Popcorn-like

Figure 65-2. Four benign patterns of nodule calcification.


V

Figure 65-3. Pulmonary arteriovenous malformation on CT. Note tubular nodular nidus in right lung (arrow) that has draining veins leading to pulmonary vein (V). Other images show enhancing feeding artery to nidus (not shown).

Figure 65-4. Invasive aspergillosis with “CT halo” sign on CT. Note partially cavitary pulmonary nodule (arrow) surrounded by faint ground-glass opacity secondary to pulmonary hemorrhage.

10. How does the degree of enhancement of pulmonary nodules on CT aid in the determination of benignancy?The degree of enhancement of pulmonary nodules is directly related to the likelihood of malignancy and the vascularity of the nodules and may be determined through CT nodule densitometry. Noduleenhancement of less than 15 HU (a measure of density) on CT after intravenous contrast agent administration is strongly predictive of benignancy, whereas enhancement of more than 15 HU may indicate either malignancy or active inflammation. False-negative enhancement studies may occur occasionally when central necrosis, cavitation, or abundant mucin is present within a pulmonary nodule or if a pulmonary nodule is very small.

11. How does FDG PET aid in the differentiation of benign and malignant lung nodules?Malignant pulmonary nodules generally have increased glucose metabolism with increased uptake, trapping, and accumulation of FDG, a radioisotopic glucose analogue that can be seen on PET. Occasionally, active inflammatory granulomatous pulmonary nodules may show increased uptake of FDG, although not as great in amount as in malignancy. Lack of FDG uptake in a pulmonary nodule measuring 10 mm or more is strongly predictive of benignancy, although malignantnodules that are due to BAC or bronchial carcinoid or that are less than 10 mm may have low or absent FDG uptake. Dual-time point FDG PET with early and delayed imaging can characterize pulmonary nodules further because malignant nodules tend to accumulate radiotracer over time, and benign nodules tend to wash out radiotracer gradually.

12. Describe some clinical features that suggest whether SPN is more likely to be malignant, and whether it is more likely to be due to lung carcinoma or a pulmonary metastasis if there is a history of extrapulmonary primary malignancy.Older patient age (>35 years old), history of prior malignancy, presence of symptoms and signs of malignancy such as hemoptysis, and history of tobacco use all increase the likelihood that
SPN is malignant rather than benign. Most patients with a history of extrapulmonary primary malignancy and SPN have a primary lung carcinoma rather than a pulmonary metastasis or benign lesion, although this varies depending on the type of primary malignancy. A metastasis as the cause of SPN in this setting is more common than primary lung carcinoma when the primary malignancy is due to melanoma, sarcoma, or testicular carcinoma. Multiplicity of pulmonary nodules also tends to make metastases more likely than lung carcinoma. Finally, primary lung carcinoma occurs more commonly in the upper lung fields, whereas pulmonary metastases occur more commonly in the lower lung fields. There are no definitive imaging criteria, however, that can fully separate a pulmonary metastasis from a primary lung carcinoma as the etiologic factor for SPN.
13. What minimally invasive procedures may be used to obtain tissue samples from SPN?Image-guided transthoracic needle biopsy is the procedure of choice for definitive characterization of peripheral pulmonary nodules, whereas bronchoscopic needle biopsy is typically used for the characterization of nodules that
involve the central airways and lungs.


14. What are potential complications of transthoracic needle biopsy?Pneumothorax is the most common complication, occurring in 25% of cases, particularly when severe emphysema is present. Nondiagnostic or false-negative biopsy results, hemoptysis, hemorrhage, pain, infection, air embolus, and tumor seeding are less common complications. Avoiding crossing pulmonary fissures with the biopsy needle or avoiding multiple lung punctures decreases the incidence of pneumothorax.

15. How important is lung carcinoma as a public health issue?Lung carcinoma is the most common cause of cancer-related death in men and women, and is the second most common cause of cancer in men after prostate cancer and in women after breast cancer. Tobacco use is the number 1 risk factor for lung carcinoma, and 85% of lung carcinoma deaths are due to smoking. The risk of developing lung carcinoma is proportional to the number of pack-years of smoking. Synchronous primary lung carcinomas occur in less than 5% of patients with lung carcinoma, but metachronous primary lung carcinomas may occur in 15%, with a latency of about 4 to 5 years. Overall, survival rates for patients with lung carcinoma are poor (<15% at 5 years), although patients with treated early-stage disease or with a BAC tumor subtype tend to have much better survival rates.

16. What are the major histologic types and subtypes of lung carcinoma?Histologically, 75% are non–small cell lung carcinomas (NSCLC), for which the prognosis primarily depends on surgical stage at diagnosis, and 25% are small cell lung carcinomas (SCLC), which behave aggressively with early and wide dissemination. NSCLC may be subdivided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma subtypes, in order of decreasing frequency. BAC is a less aggressive subtype of adenocarcinoma that spreads along preexisting alveolar septa without lung parenchymal invasion.

17. Summarize some of the differing features of the various histologic types and subtypes of lung carcinoma.• Adenocarcinoma is the subtype least closely associated with tobacco use and tends to develop in the lung periphery,

whereas squamous cell carcinoma is strongly associated with tobacco use, tends to develop centrally within a lobar or segmental bronchus, and is often cavitary.

• Large cell carcinoma is a histologic diagnosis of exclusion among the subtypes of lung carcinoma, is strongly associated with tobacco use, and often manifests as a large peripheral lung mass. Small cell lung carcinoma usually arises centrally within the chest with extensive metastatic lymphadenopathy involving the hila and mediastinum and only rarely cavitates, but it may manifest in a more limited form in one hemithorax or as SPN.

18. What is a superior sulcus tumor?Superior sulcus tumor (or Pancoast tumor) usually refers to a primary lung carcinoma that is located in the lung apex and involves the adjacent pleura, chest wall, brachial plexus, or subclavian vessels (Fig. 65-5). Typically, this tumor manifests clinically as chest, shoulder, and arm pain with paresthesias, along with Horner syndrome (ipsilateral ptosis, miosis, and anhidrosis) caused by invasion of the stellate ganglion. Squamous cell carcinoma is the most common subtype involved, and adenocarcinoma is the second most common.

19. Describe the major imaging findings related to lung carcinoma.• A pulmonary or endobronchial nodule or mass is seen that may be associated with obstructive atelectasis or pneumonitis;

thoracic lymphadenopathy; pleural, mediastinal, or chest wall involvement; or distant metastatic disease (Fig. 65-6).

A

T

T

B C

Figure 65-5. A, Pancoast tumor secondary to NSCLC on chest radiograph. Note right apical pulmonary tumor (T ) with lobulated margins. B, Pancoast tumor secondary to NSCLC on CT. Note soft tissue attenuation right apical pulmonary tumor (T ). C, Pancoast tumor secondary to NSCLC on FDG PET. Note avid FDG uptake in right apical pulmonary tumor (arrow).


Figure 65-8. BAC subtype of NSCLC on CT. Note SPN (arrow) in right lung with cystic or cavitary change.

A

T

P

B

Figure 65-6. A, Unresectable NSCLC associated with malignant pleural effusion on chest radiograph. Note soft tissue fullness in right hilum along with obscuration of right hemidiaphragm owing to large right pleural effusion. B, Unresectable NSCLC associated with malignant pleural effusion on FDG PET/CT. Note soft tissue tumor (T ) in right hilum along with large loculated right pleural effusion (P ) that has areas of FDG uptake.

Figure 65-7. NSCLC causing lobar atelectasis with “(reverse) S sign of Golden” on chest radiograph. Note right upper lobe obstructive atelectasis with S-shaped fissural margin with focal convexity centrally owing to central mass and concavity more distally. Note lack of air bronchograms typical of obstructive atelectasis.

• Sometimes, obstructive segmental or lobar atelectasis may be the only sign of lung carcinoma on chest radiography, particularly if associated air bronchograms are not present. When obstructive atelectasis is associated with focal convexity centrally owing to the nodule or mass with concavity more distally on chest radiography, an S-shaped smooth fissural margin may be seen that is known as the “S sign of Golden” (Fig. 65-7).

• Unilateral hilar lymphadenopathy; a unilateral pleural effusion (particularly when present on the left); abrupt cutoff of a bronchus (the “bronchial cutoff” sign); and obscuration of a hilar, mediastinal, or diaphragmatic structure (the “silhouette” sign) are other chest radiographic findings of pulmonary malignancy. BAC may appear as a solitary nodule; multiple ground-glass, solid, or mixed-density pulmonary nodules; or solitary, multiple, or diffuse foci of chronic pulmonary consolidation. Cavitation or cystic change may be present (Fig. 65-8).

20. Summarize the tumor node metastasis (TNM) staging system for NSCLC.See Table 65-2.

21. When is NSCLC generally considered unresectable?When NSCLC is stage IIIb (i.e., with the presence of invasion of vital mediastinal structures, associated malignant pleural effusion, satellite tumor in the primary tumor lobe, or unresectable lymphadenopathy) or stage IV (i.e., with the presence of distant metastases), it is generally considered unresectable. Symptoms and signs are rarely present until the disease is advanced in stage and more likely to be unresectable.


Table 65-2. TNM Staging System of Non–Small Cell Lung CarcinomaT = Primary Tumor

T0 No evidence of primary tumor

T1 ≤3 cm, surrounded by lung/visceral pleural, no invasion of main stem bronchus

T2 >3 cm, involvement of main stem bronchus ≥2 cm from carina, invasion of visceral pleura; obstructive atelectasis of part of the lung

T3 Invasion of chest wall, mediastinal pleura, diaphragm, parietal pericardium, main stem bronchus <2 cm from carina; obstructive atelectasis of entire lung

T4 Invasion of mediastinal structures, malignant pleural effusion, or satellite tumor in primary tumor lobe

N = Regional Lymphadenopathy

N0 No regional lymph node metastases

N1 Ipsilateral hilar, peribronchial, or intrapulmonary lymphadenopathy

N2 Ipsilateral mediastinal or subcarinal lymphadenopathy

N3 Supraclavicular, scalene, contralateral mediastinal, or hilar lymphadenopathy

M = Distant Metastasis

M0 No distant metastasis

M1 Distant metastasis

Stage

0 Carcinoma in situ

Ia T1N0M0

Ib T2N0M0

IIa T1N1M0

IIb T2N1M0, T3N0M0

IIIa T3N1M0, T1-3N2M0

IIIb T4N0-3M0, T1-3N3M0

IV T0-4N0-3M1

Note: Any N2 lesion is at least stage IIIa, any T4 or N3 lesion is at least stage IIIb, and any M1 lesion is stage IV. Patients with stage 0 to IIIa lesions are generally treated with surgery, whereas patients with stage IIIb and IV lesions are generally treated with medical therapy.

22. Are there any reliable screening tests for lung carcinoma? What is the National Lung Screening Trial (NLST)?At this time, no laboratory or imaging screening test has been shown to decrease lung cancer mortality rates. NLST is an ongoing multicenter prospective trial that is comparing screening with frontal chest radiography with screening with thin-section, low-dose chest CT for a decrease in lung cancer–specific mortality. The trial is expected to be concluded in 2011. Research is also currently ongoing in the search for biomarkers that could potentially be used as screening tools for the presence of lung carcinoma or as indicators of high risk for future development of lung carcinoma.

Key Points: Pulmonary Nodules

1. Be aware of the major blind spots on frontal chest radiography: the lung apices where the clavicles and ribs overlap, the hilar regions where vascular structures abound, the retrocardiac region, and the lung bases where there is superimposition with the upper abdominal soft tissue.

2. If you see lobar or segmental atelectasis on chest radiography, particularly without air bronchograms, be suspicious of an obstructive endobronchial lesion such as a lung carcinoma, and, at the minimum, get a short-term follow-up chest radiograph.

3. If a pulmonary infiltrate does not resolve over time despite treatment with antimicrobial agents, be suspicious of a potential bronchioloalveolar cell subtype of lung carcinoma.

4. The best way to prevent lung cancer is through prevention (i.e., by not smoking).5. Although mucoid impaction of a bronchus may mimic a pulmonary nodule on chest

radiography, one should exclude an endobronchial lesion as the cause for mucus retention in a bronchus if resolution is not seen on follow-up imaging.


Figure 65-9. Pulmonary metastases are CT. Note multiple, variably sized, smoothly marginated nodules throughout lungs.

23. Name some treatment options for lung carcinoma.Surgical resection (typically lobectomy with lymph node resection), chemotherapy, and radiation therapy may be used depending on the stage of disease and the histology of the tumor. Cessation of tobacco use is also part of treatment. Newer techniques such as percutaneous ablation of focal lung or bronchial tumors are currently under investigation.

24. Describe the imaging findings of pulmonary metastases.Solitary or multiple pulmonary and endobronchial nodules or masses are often seen (Fig. 65-9), which may be ill-defined or well circumscribed, ground-glass or solid in density, and often associated with metastases to other thoracic or extrathoracic anatomic locations. Depending on the underlying primary malignancy, the lesions may be
homogeneous or heterogeneous with cystic, necrotic, calcific, or hemorrhagic change, and may vary in size from very small (miliary) nodules to very large “cannonball” masses. Pneumothorax is often associated with pulmonary metastatic disease from osteogenic sarcoma. Overall, the lungs are an extremely common site of metastatic disease.
25. What is lymphangitic carcinomatosis?Lymphangitic carcinomatosis is the hematogenous spread of metastatic disease to lung interstitium with subsequent lymphatic obstruction, interstitial edema, and fibrosis. Primary tumors of the breast, lung, stomach, pancreas, ovary, and cervix are often associated with lymphangitic carcinomatosis. On chest radiography, the lungs may appear clear, or they may show a central linear pattern of interstitial thickening that is commonly bilateral, but asymmetric in distribution between the lungs. On CT, typical smooth or nodular thickening of the interlobular septa is seen often with peribronchovascular thickening and asymmetric involvement of the lungs bilaterally (Fig. 65-10).

26. What are pulmonary carcinoid tumors?These are rare neuroendocrine neoplasms that range from low-grade typical carcinoids to more aggressive atypical carcinoids. They are not related to tobacco use and occur slightly more commonly in women. Most arise centrally in an endobronchial location and are commonly associated with segmental or lobar obstructive atelectasis or pneumonitis, whereas the remainder appear as well-circumscribed peripheral pulmonary nodules or masses. These lesions typically show avid enhancement, and 40% may be associated with internal calcification. Carcinoid syndrome is rarely associated with pulmonary carcinoid tumors.

27. What is a pulmonary hamartoma?Pulmonary hamartoma is the most common benign neoplasm of the lung and typically manifests as an asymptomatic well-circumscribed SPN, typically during the fourth through seventh decades of life. Pathologically, these are

A BB

T

Figure 65-10. A, Lymphangitic carcinomatosis in NSCLC on CT. Note smooth asymmetric thickening of interlobular septa (arrows) in right lung. B, Lymphangitic carcinomatosis in NSCLC on CT. Note large cavitary tumor (T ) in right lung secondary to lung carcinoma.


mesenchymal tumors that have foci of mature cartilage separated by islands of fat and bronchial epithelium, often with fibrosis, calcification, or ossification. Typical CT findings include a smoothly marginated SPN that often contains visible fat or dense foci of calcification or ossification or both.

28. What is congenital bronchial atresia?Congenital bronchial atresia is due to atresia or stenosis of a bronchus at or near its origin, most often seen in the apicoposterior segment of the left upper lobe. Imaging findings include hyperlucency with air trapping and decreased vascularity to the portion of lung supplied by the involved bronchus, along with a nonenhancing hilar mass (bronchocele) or nonenhancing branching soft tissue opacities usually with bronchial dilation owing to mucoid impaction. Congenital bronchial atresia can appear as SPN on chest radiography.

BiBliography

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[2] A. Jemal, R.C. Tiwari, T. Murray, et al., Cancer statistics, 2004, CA Cancer. J. Clin. 54 (2004) 8–29.[3] J.L. Leef 3rd, J.S. Klein, The solitary pulmonary nodule, Radiol. Clin. North Am. 40 (2002) ix 123–143.[4] A. Matthies, M. Hickeson, A. Cuchiara, A. Alavi, Dual time point 18F-FDG PET for the evaluation of pulmonary nodules, J. Nucl. Med.

43 (2002) 871–875.[5] S. Takashima, S. Sone, F. Li, et al., Small solitary pulmonary nodules (l1 cm) detected at population-based CT screening for lung cancer:

reliable high-resolution CT features of benign lesions, AJR Am. J. Roentgenol. 180 (2003) 955–964.[6] B.B. Tan, K.R. Flaherty, E.A. Kazerooni, M.D. Iannettoni, The solitary pulmonary nodule, Chest 123 (2003) 89S–96S.[7] A.W. Tang, H.A. Moss, R.J. Robertson, The solitary pulmonary nodule, Eur. J. Radiol. 45 (2003) 69–77.

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