AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Patients with solitary pulmonary nodules (SPNs) are usually asymptomatic; however, SPNs pose a challenge to both physicians and patients. Whether detected serendipitously or during a routine investigation, a nodule on a chest radiograph raises several questions: Is the nodule benign or malignant? Should it be investigated or observed? Should it be surgically resected?

Most SPNs are benign, but they may represent an early stage of lung cancer. Lung cancer is the leading cause of cancer death in the United States, accounting for more deaths annually than breast, colon, and prostate cancers combined. Lung cancer survival rates remain dismally low at 14% at 5 years. Early lung cancer, when the primary tumor is less than 3 cm in diameter (stage 1A), may lead to 5-year survival rates of 70-80%. Therefore, prompt diagnosis and management of early lung cancer manifesting as SPN may be the only chance for cure.

Pathophysiology

An SPN is defined as a single, discrete pulmonary opacity that is less than 3 cm in diameter, surrounded by normal lung tissue, and not associated with adenopathy or atelectasis.

Generally, a pulmonary nodule must reach 1 cm in diameter before it can be identified on a chest radiograph. For a malignant nodule to reach this size, approximately 30 doublings would have occurred. The average doubling time for a tumor is 120 days (range, 7-590 d). A lesion at this growth rate may be present for 10 years before discovery.

An SPN may be secondary to one of the numerous differential diagnoses listed in Causes. However, more than 95% are neoplasms (most likely primary), granulomas (most likely infectious), or benign lesions (most likely hamartoma).

Frequency

United States

SPNs are one of the most common thoracic radiographic abnormalities. Approximately 150,000 cases are detected each year as an incidental finding, either on images from chest radiographs or images from thoracic CT scans (Lillington, 1991). Approximately 40-50% of these nodules are malignant. Most are bronchogenic carcinoma, but 10-30% may be solitary metastases.

Mortality/Morbidity

Most SPNs are benign, but they may represent an early stage of lung cancer.

• While lung cancer survival rates remain dismally low at 14% at 5 years, early lung cancer, ie, diagnosed when the primary tumor has a diameter smaller than 3 cm (stage 1A), can be associated with a 5-year survival rate of 70-80%.
• Accordingly, the only chance for cure of early lung cancer manifesting as SPN is prompt diagnosis and management.

Age

Risk of malignancy increases with age.

• For individuals younger than 39 years, the risk is 3%.
• The risk increases to 15% for individuals aged 40-49 years, to 43% for persons aged 50-59 years, and to more than 50% for persons older than 60 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Patients with solitary pulmonary nodules (SPNs) are asymptomatic; the nodules are typically detected as an incidental finding. Approximately 20-30% of all bronchogenic carcinomas appear as SPNs on initial radiographs. The following features are important when assessing whether the nodule is benign or malignant.

• History of smoking
• History of malignancy
• Travel: Travel to areas with endemic mycosis (eg, histoplasmosis, coccidioidomycosis, blastomycosis) or to areas with a high prevalence of tuberculosis (TB) can lead to the development of a benign SPN.
• Occupational risk factors for lung cancer: Exposure to asbestos, radon, nickel, chromium, vinyl chloride, and polycyclic hydrocarbons can lead to acquisition of an SPN.
• History of TB or pulmonary mycosis

Causes

Bearing in mind that the major distinction that must be made is between neoplastic and inflammatory lesions, SPNs may have the following causes:

• Neoplastic (malignant or benign)
• • Bronchogenic carcinoma
  • Metastasis
  • Lymphoma
  • Carcinoid
  • Hamartoma
  • Connective tissue and neural tumors - Fibroma, neurofibroma, blastoma, sarcoma
• Inflammatory (infectious)
• • Granuloma - TB, histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, nocardiosis
  • Lung abscess
  • Round pneumonia
  • Hydatid cyst
• Inflammatory (noninfectious)
• • Rheumatoid arthritis
  • Wegener granulomatosis
  • Sarcoidosis
  • Lipoid pneumonia
• Congenital
• • Arteriovenous malformation
  • Sequestration
  • Lung cyst
• Miscellaneous
• • Pulmonary infarct
  • Round atelectasis
  • Mucoid impaction
  • Progressive massive fibrosis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory studies have a limited role in the workup of solitary pulmonary nodules (SPNs).
• • Anemia or an elevated sedimentation rate may indicate an underlying neoplastic or infectious process.
  • Elevated levels of liver enzymes, alkaline phosphatase, or serum calcium may indicate metastases from the solitary bronchogenic carcinoma or extrapulmonary malignancy. Patients who have histoplasmosis or coccidioidomycosis may have high levels of immunoglobulin G and immunoglobulin M antibodies specific to these fungi.

Imaging Studies

• Chest radiography
• • Because SPNs are first detected on chest radiographs, the initial decision is whether the nodule is pulmonary or extrapulmonary in nature. Findings from a lateral chest radiograph, fluoroscopy, or CT scan may help confirm the location of the nodule.
  • Although nodules of 5 mm in diameter are occasionally visualized on chest radiographs, SPNs are quite often 8-10 mm in diameter.
  • The most important question is whether malignancy is unlikely or impossible or if malignancy remains a serious consideration.
  • Chest radiographs can provide information regarding size, shape, cavitation, growth rate, and calcification pattern. All of these radiologic features can help determine whether the lesion is benign or malignant. However, none of these features is entirely specific for lung carcinoma.
  • Radiologic characteristics that may help establish the diagnosis with reasonable certainty include (1) a benign pattern of calcification, (2) a growth rate that is either too slow or too fast for lung cancer, (3) a specific shape or appearance of the nodule consistent with that of a benign lesion, and (4) unequivocal evidence of another benign process.
    • Size and shape: Although a well-defined nodule of smaller size that is clearly visible on chest radiographs may be calcified and benign, most smaller lesions are probably early-stage bronchogenic carcinoma. A lesion more than 4 cm in diameter is very likely a bronchogenic carcinoma, although exceptions include lung abscess, Wegener granulomatosis, lymphoma, round pneumonia, rounded atelectasis, and hydatid cyst. The shape of a nodule is generally not helpful in determining the cause; however, a few specific patterns may indicate an underlying diagnosis. A very irregular edge or corona radiata (numerous strands radiating into the surrounding lung) may indicate a bronchogenic carcinoma. A well-defined, smooth, nonlobulated edge may indicate a benign lesion or metastasis, whereas lobulation and notching may indicate bronchogenic carcinoma.
    • Rate of growth: Serial chest radiographs facilitate estimation of the growth rate of a nodule. Growth rate refers to the doubling time of a nodule, which is doubling of the nodule volume. Because a nodule on a chest radiograph is seen as a 2-dimensional circle rather than a 3-dimensional sphere, an increase in diameter of 26% corresponds to a doubling of nodule volume. Bronchogenic carcinoma generally doubles in 1-18 months (average 4-8 mo). Although a doubling time of less than 1 month or longer than 18 months makes bronchogenic carcinoma unlikely, it does not exclude the diagnosis completely. Doubling times of less than 1 month suggest infections; doubling times of more than 18 months suggest benign processes such as granuloma, hamartoma, bronchial carcinoid, and rounded atelectasis. If a nodule remains the same size for 2 years, it is very likely benign; however, further follow-up monitoring may be indicated.
    • Calcification: Chest radiographs may demonstrate calcification, which often indicates that the lesion is benign. (The CT scan is the most sensitive technique for detection of calcification.) The 5 patterns of calcification usually observed in benign lesions are diffuse, central, laminar, concentric, and popcorn. A stippled or eccentric pattern is associated with malignancy.
    • Other chest radiographic features that may help determine whether a nodule is benign or malignant: The presence of air bronchograms within the SPN makes bronchogenic carcinoma or metastasis unlikely, although they may be observed with bronchoalveolar carcinoma or lymphoma. Invasion of the adjacent bone by the nodule is pathognomic of bronchogenic carcinoma. Cavitation with a thin, smooth wall may indicate lung abscess or a benign lesion, whereas thick-walled cavitations imply an underlying malignant neoplasm.
• Computed tomography
• • CT scan of the chest has many advantages over the plain chest radiograph. Advantages include better resolution of nodules and detection of nodules as small as 3-4 mm. CT scan images also help better characterize the morphologic features of various lesions. Multiple nodules and regions that are difficult to assess on chest radiographs are better visualized on CT scan images.
  • CT densitometry measures the attenuation coefficients of a lesion and aids detection of occult calcification. Attenuation coefficients are expressed in Hounsfield units (HU); a value of more than 185 HU has been suggested as a cutoff for benign lesions. However, prospective studies have indicated low sensitivity and specificity for CT densitometry measurements. Combining densitometry with other clinical and radiological features may provide useful clinical information.
  • Other CT scan features indicative of a benign lesion include the demonstration of fat within a nodule. This is specific for a benign lesion (ie, hamartoma). Also, CT scan helps distinguish lung abscess from empyema, particularly if a cavity exists within the lesion.
  • CT halo sign, ie, ground-glass attenuation surrounding a nodule on CT scan image, most commonly indicates infection with an invasive Aspergillus species. Other less common possibilities include TB, cytomegalovirus infection, or herpes simplex infections.
  • A greater degree of contrast enhancement on repeated measurements of attenuation indicates that the nodule is malignant. Enhancement of greater than 20 HU is associated with malignancy, whereas less than 15 HU suggests a benign lesion. Active granulomas or other infectious lesions may also enhance, thus limiting the application of this technique. However, a failure to enhance by more than 15-20 HU has greater than a 95% predictive value for benignity.
• Positron emission tomography
• • Because malignant nodules have increased glucose metabolism compared to benign lesions and normal lung, enhancement of the lesion makes it likely to be malignant.
  • Several studies have reported the sensitivity of fluorodeoxyglucose (FDG) positron emission tomography (PET) scan to be more than 90%, with a specificity of more than 90%. Injection of glucose of analogue 18-F-2 fluorodeoxyglucose is used to assess the metabolic activity. FDG-PET scans may be analyzed semiquantitatively using standardized uptake values (SUVs) to normalize measurements for the patient's weight and the injected dose of radioisotope.
  • Although visual analysis findings (depending on experience and judgment of the nuclear medicine physician) may match SUV calculations, an SUV of less than 2.5 is considered indicative of a benign lesion.
  • FDG-PET scans are quite helpful in detecting mediastinal metastases, thus improving staging of noninvasive lung cancer.
  • FDG-PET scans have several limitations because the false-positive findings occur in other metabolically active pulmonary nodules, which are either infectious or inflammatory. Tumors that have lower metabolic rates, such as carcinoid and bronchoalveolar carcinoma, may be difficult to distinguish from background activity. Finally, the FDG-PET scan has lower sensitivity for nodules smaller than 20 mm in diameter and may miss lesions smaller than 10 mm.
  • A meta-analysis of 40 studies evaluated 1474 focal pulmonary lesions of any size. The sensitivity and specificity were 96.8% and 77.8%, respectively. Positron emission tomography with 18-fluorodeoxyglucose (FDG) is an accurate noninvasive imaging test for the diagnosis of pulmonary nodules and larger mass lesions as FDG-PET has high sensitivity and intermediate specificity for malignancy. However, not much data are available for nodules smaller than 1 cm in diameter.
  • A study recently compared the diagnostic accuracy of helical dynamic CT (HDCT) and integrated PET/CT for pulmonary nodule characterization. The sensitivity, specificity, and accuracy for malignancy on HDCT were 81% (64/79 nodules), 93% (37/40), and 85% (101/119), respectively, whereas those on integrated PET/CT were 96% (76/79), 88% (35/40), and 93% (111/119), respectively. Integrated PET/CT is more sensitive and accurate than HDCT for the malignant nodule diagnosis, making it the first-line evaluation tool for SPN evaluation. Because of the high specificity and acceptable sensitivity and accuracy of HDCT, it may be a reasonable alternative when PET/CT is unavailable.
• Single-photon emission computed tomography
• • Single-photon emission computed tomography (SPECT) scans are less expensive than PET scans but have comparable sensitivity and specificity.
  • SPECT imaging is performed using a radiolabeled somatostatin-type receptor binder, technetium Tc P829.
  • SPECT imaging has not been evaluated in a large series of patients; in a smaller series, the sensitivity fell significantly for nodules less than 20 mm in diameter.
  • Naalsund et al evaluated the diagnostic performances of technetium-99m (Tc-99m) depreotide in differentiating benign SPNs from malignant SPNs. They also compared the diagnostic accuracy of Tc-99m with fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in a prospective, multicenter trial. SPECT scan Tc-99m depreotide revealed a sensitivity, specificity, and diagnostic accuracy of 89%, 67%, and 81%, respectively. Furthermore, in patients who underwent both Tc-99m depreotide SPECT and FDG-PET imaging, sensitivity, specificity, and diagnostic accuracy were identical for both modalities.

Procedures

• Biopsy
• • Biopsy of an SPN can be performed bronchoscopically or via transthoracic needle aspiration (TTNA). Because the yield from bronchoscopy is only 10-20% when the nodule is less than 2 cm in diameter, bronchoscopy and transbronchial needle aspiration (TBNA) may be helpful when the lesion is either endobronchial in location or near a large airway. TBNA may also be helpful in sampling the mediastinal nodes.
  • TTNA reportedly has an accuracy of 90-95% when the lesion is 2 cm or larger in diameter, although the diagnosis is less accurate (60-80%) in lesions smaller than 2 cm. Confirming a specific benign diagnosis is more difficult (~70% accuracy); therefore, most lesions are characterized as nondiagnostic following TTNA.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Comparison of a nodule to a previous chest radiograph is the most important and cost-effective initial step in the evaluation of a solitary pulmonary nodule (SPN). An absence of growth over a 2-year period indicates benignity. Reexamination of 2 years of stability data demonstrates that the predictive value for a benign diagnosis is only 65%; therefore, annual observation for up to 5 years may be prudent. Because assessing the growth rate of a nodule smaller than 1 cm in diameter may be difficult, use CT scanning to monitor these patients.

• If the nodule shows none of the features associated with benignity, use thin-section CT scanning and CT densitometry and contrast enhancement. When 10% of the nodule on CT densitometry images shows calcification, the probability of cancer is low and these patients can be monitored with repeat studies. Otherwise, the presence of occult calcification must be interpreted with caution. Patients with nodule enhancement of less than 15 HU can be monitored with serial radiographs.
• Nodules deemed indeterminate following CT scan may be evaluated with FDG-PET scanning or SPECT scanning; however, both of these techniques are relatively nonspecific and have not been widely used.
• Use TTNA in indeterminate nodules or when malignancy is quite unlikely (eg, a young person who does not smoke). For situations in which the risk of pulmonary resection outweighs the potential benefit of removal of a malignancy, TTNA may help establish a definitive diagnosis.

Surgical Care

• When a lesion is likely to be malignant, surgical resection—not TTNA or observation—is often used. Thoracotomy is generally performed when the lesion is 3 cm from visceral pleura or if a nodule is fairly small. However, localization using methylene blue injection and wire placement has facilitated successful resection of smaller nodules with video-assisted thoracoscopic surgery (VATS). Intraoperative ultrasonography is also suggested as a means of nodule localization during VATS.
• Previous reports indicate a higher incidence of pneumothorax following TTNA (Lacasse, 1999). Approximately 1 in 3 procedures require chest tube placement in half of these patients. The more recent series reports the need for chest tube placement in approximately 10% of patients who developed pneumothorax following TTNA (Klein, 2000).

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Recommended follow-up schedule for solitary pulmonary nodules (SPNs)
• • Obtain chest radiographs at 3-month intervals for the first 12 months and then at 6-month intervals for the next 12 months.
  • After this 2-year period, SPNs may be observed yearly for up to 5 years.

Deterrence/Prevention

• Avoiding possible causes may help prevent SPN formation. Possible avoidable causes include the following:
• • Smoking
  • Travel to areas endemic for mycosis (eg, histoplasmosis, coccidioidomycosis, blastomycosis) or to areas with a high prevalence of tuberculosis
  • Occupational exposure to risk factors for lung cancer (eg, asbestos, radon, nickel, chromium, vinyl chloride, polycyclic hydrocarbons)

Complications

• Most SPNs are benign, but they may represent an early stage of lung cancer. While lung cancer survival rates remain dismally low at 14% at 5 years, early lung cancer, ie, diagnosed when the primary tumor has a diameter smaller than 3 cm (stage 1A), can be associated with a 5-year survival rate of 70-80%. Accordingly, the only chance for cure of early lung cancer manifesting as SPN is prompt diagnosis and management.

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Because a malignancy may be curable when present as a solitary pulmonary nodule (SPN), take great care in evaluating such masses.
• A comprehensive assessment generally includes history, physical examination, evaluation of previous chest radiographs, incorporation of other imaging studies (eg, CT scan, PET scan, SPECT scan), and invasive diagnostic procedures.
• Because TTNA may be associated with risks and complications, informed consent must be obtained.
• The most important question while evaluating an SPN is whether the lesion is benign or malignant. An estimate of the probability of benignity might be an effective strategy. The Bayes theorem combines the radiologic features of a nodule and clinical findings of an individual patient to estimate the probability of malignancy.
• • The radiographic features of SPNs included in the Bayes analysis are size, edge, contour, cavity-wall thickness, and growth rate; the clinical parameters are smoking, age, previous malignancy, and hemoptysis. (These features and parameters have been derived from previously published series.)
  • The calculation of likelihood ratios and their use may result in fewer false-negative and false-positive results (Cummings, 1986).
• The probability of malignancy only provides an estimation based on previously published studies and may not be generalized to an individual patient; therefore, patient preferences and clinician experience are important in planning further management strategies.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Solitary pulmonary nodule. Right upper lobe nodule shows peripheral calcification and high Hounsfield unit enhancement, suggesting that the lesion is a calcified benign pulmonary nodule.
	View Full Size Image
Media type:  CT

Media file 2:  Solitary pulmonary nodule. A 1.5-cm coin lesion in the left upper lobe in a patient with prior colonic carcinoma. Transthoracic needle biopsy findings confirmed this to be a metastatic deposit.
	View Full Size Image
Media type:  CT

Media file 3:  Solitary pulmonary nodule. Mediastinal windows of the case in Image 2.
	View Full Size Image
Media type:  CT

Media file 4:  Solitary pulmonary nodule. Right lower lobe nodule demonstrating central calcification. The most likely diagnosis is histoplasmosis.
	View Full Size Image
Media type:  X-RAY

Media file 5:  Solitary pulmonary nodule. Close-up view of the chest x-ray film in Image 4.
	View Full Size Image
Media type:  X-RAY

Media file 6:  Solitary pulmonary nodule. Left upper lobe cavitating solitary nodule eventually identified as active pulmonary tuberculosis from percutaneous needle biopsy findings.
	View Full Size Image
Media type:  X-RAY

Media file 7:  Solitary pulmonary nodule. A left upper lobe nodule with central lucency and poorly circumscribed margins was diagnosed as actinomycosis based on needle biopsy findings.
	View Full Size Image
Media type:  X-RAY

Media file 8:  Solitary pulmonary nodule. CT scan of the patient presented in Image 7. After needle biopsy, the presence of classic sulfur granules confirmed actinomycosis.
	View Full Size Image
Media type:  CT

Media file 9:  A right lower lobe solitary pulmonary nodule later identified to be a hamartoma.
	View Full Size Image
Media type:  X-RAY

Media file 10:  Solitary pulmonary nodule. Wedge-shaped peripheral (pleural based) density observed secondary to pulmonary infarction (pulmonary embolism). This is termed the Westermark sign.
	View Full Size Image
Media type:  CT

Media file 11:  Solitary pulmonary nodule. Left upper lobe 1.5-cm nodule shows negative CT scan numbers, suggesting fat in the lesion consistent with hamartoma.
	View Full Size Image
Media type:  CT

Media file 12:  Solitary pulmonary nodule. A left upper lobe solitary pulmonary nodule. The differential diagnosis is large, but CT scan findings help narrow the differentials and establish the diagnosis.
	View Full Size Image
Media type:  X-RAY

Media file 13:  Solitary pulmonary nodule. Cavitating right lower lobe nodule later confirmed to be primary pulmonary lymphoma. Calcium deposits may also be present in the lesion.
	View Full Size Image
Media type:  X-RAY

Media file 14:  Solitary pulmonary nodule. This left lower lobe carcinoid tumor was quite bloody after a percutaneous needle biopsy was performed.
	View Full Size Image
Media type:  X-RAY

Media file 15:  Solitary pulmonary nodule. A lateral radiograph of the case in Image 14.
	View Full Size Image
Media type:  X-RAY

Media file 16:  Solitary pulmonary nodule. CT scan of the patient in Image 14 shows a well-circumscribed lesion.
	View Full Size Image
Media type:  CT

Media file 17:  Solitary pulmonary nodule. A "popcorn" calcification in the left lung nodule indicates a benign lesion or hamartoma. No further tests or observations are needed for this patient.
	View Full Size Image
Media type:  X-RAY

Media file 18:  Solitary pulmonary nodule. A 1.5 cm right upper lobe nodule on CT scan was determined to be a benign fibrous lesion on needle biopsy. A follow-up at 2 years showed no change in the size of this lesion.
	View Full Size Image
Media type:  CT

Media file 19:  The parenchymal lesion in this CT scan demonstrates low attenuation within the lesion, indicating the presence of fat. Fat density is only observed in hamartoma and lipoid pneumonia. The likely diagnosis is hamartoma.
	View Full Size Image
Media type:

Media file 20:  This patient has a low risk for the right upper lobe nodule to be malignant; therefore, continued observation with repeat chest radiographs to establish a growth pattern is the best treatment option
	View Full Size Image
Media type:

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

• Chhajed PN, Bernasconi M, Gambazzi F. Combining bronchoscopy and positron emission tomography for the diagnosis of the small pulmonary nodule < or = 3 cm. Chest. Nov 2005;128(5):3558-64.
• Chung T. Fine needle aspiration of the solitary pulmonary nodule. Semin Thorac Cardiovasc Surg. Jul 2002;14(3):275-80. [Medline].
• Cummings SR, Lillington GA, Richard RJ. Estimating the probability of malignancy in solitary pulmonary nodules. A Bayesian approach. Am Rev Respir Dis. Sep 1986;134(3):449-52. [Medline].
• Decamp MM Jr. The solitary pulmonary nodule: aggressive excisional strategy. Semin Thorac Cardiovasc Surg. Jul 2002;14(3):292-6. [Medline].
• Erasmus JJ, Connolly JE, McAdams HP, Roggli VL. Solitary pulmonary nodules: Part I. Morphologic evaluation for differentiation of benign and malignant lesions. Radiographics. Jan-Feb 2000;20(1):43-58. [Medline].
• Erasmus JJ, McAdams HP, Connolly JE. Solitary pulmonary nodules: Part II. Evaluation of the indeterminate nodule. Radiographics. Jan-Feb 2000;20(1):59-66. [Medline].
• Ginsberg RJ. The solitary pulmonary nodule: can we afford to watch and wait?. J Thorac Cardiovasc Surg. Jan 2003;125(1):25-6. [Medline].
• Goldsmith SJ, Kostakoglu L. Role of nuclear medicine in the evaluation of the solitary pulmonary nodule. Semin Ultrasound CT MR. Apr 2000;21(2):129-38. [Medline].
• Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. Feb 21 2001;285(7):914-24. [Medline].
• Gould MK, Lillington GA. Strategy and cost in investigating solitary pulmonary nodules. Thorax. Aug 1998;53 Suppl 2:S32-7. [Medline].
• Gould MK, Maclean CC, Kuschner WG. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA. Feb 21 2001;285(7):914-24. [Medline].
• Hartman TE. Radiologic evaluation of the solitary pulmonary nodule. Radiol Clin North Am. May 2005;43(3):459-65, vii.
• Herder GJ, van Tinteren H, Golding RP. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest. Oct 2005;128(4):2490-6.
• Jain P, Kathawalla SA, Arroliga AC. Managing solitary pulmonary nodules. Cleve Clin J Med. Jun 1998;65(6):315-26. [Medline].
• Klein JS, Zarka MA. Transthoracic needle biopsy. Radiol Clin North Am. Mar 2000;38(2):235-66, vii. [Medline].
• Lacasse Y, Wong E, Guyatt GH, Cook DJ. Transthoracic needle aspiration biopsy for the diagnosis of localised pulmonary lesions: a meta-analysis. Thorax. Oct 1999;54(10):884-93. [Medline].
• Laurent F, Remy J. [Management strategy of pulmonary nodules]. J Radiol. Dec 2002;83(12 Pt 1):1815-21. [Medline].
• Lillington GA, Caskey CI. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med. Mar 1993;14(1):111-9. [Medline].
• Lillington GA. Solitary pulmonary nodules: new wine in old bottles. Curr Opin Pulm Med. Jul 2001;7(4):242-6. [Medline].
• Lillington GA. Management of solitary pulmonary nodules. How to decide when resection is required. Postgrad Med. Mar 1997;101(3):145-50. [Medline].
• Lillington GA. Management of solitary pulmonary nodules. Dis Mon. May 1991;37(5):271-318. [Medline].
• Moses DA, Ko JP. Multidetector CT of the solitary pulmonary nodule. Semin Roentgenol. Apr 2005;40(2):109-25. [Medline].
• Naalsund A, Maublant J. The Solitary Pulmonary Nodule - Is It Malignant or Benign? Diagnostic Performance of Tc-Depreotide SPECT. Respiration. May 5 2006.
• Ost D, Fein A. Evaluation and management of the solitary pulmonary nodule. Am J Respir Crit Care Med. Sep 2000;162(3 Pt 1):782-7. [Medline].
• Pepe G, Rossetti C, Sironi S. Patients with known or suspected lung cancer: evaluation of clinical management changes due to 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) study. Nucl Med Commun. Sep 2005;26(9):831-7.
• Plachcinska A, Mikolajczak R, Kozak J. A visual and semi-quantitative assessment of (99m)Tc-EDDA/HYNIC-TOC scintigraphy in differentiation of solitary pulmonary nodules. Nucl Med Rev Cent East Eur. 2004;7(2):143-50.
• Pogodina VV. Elizaveta Nilolaevna Levkovich-75th birthday. Acta Virol. Nov 1975;19(6):509. [Medline].
• Schaefer JF, Schneider V, Vollmar J. Solitary pulmonary nodules: Association between signal characteristics in dynamic contrast enhanced MRI and tumor angiogenesis. Lung Cancer. May 9 2006.
• Schiavon F, Berletti R, Soardi GA. Multidisciplinary management of the solitary pulmonary nodule (SPN): our opinion. Radiol Med (Torino). Sep 2005;110(3):149-55.
• Shaham D, Guralnik L. The solitary pulmonary nodule: radiologic considerations. Semin Ultrasound CT MR. Apr 2000;21(2):97-115. [Medline].
• Siegelman SS, Zerhouni EA, Leo FP, et al. CT of the solitary pulmonary nodule. AJR Am J Roentgenol. Jul 1980;135(1):1-13. [Medline].
• Swensen SJ, Silverstein MD, Ilstrup DM, et al. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. Apr 28 1997;157(8):849-55. [Medline].
• Tan BB, Flaherty KR, Kazerooni EA. The solitary pulmonary nodule. Chest. Jan 2003;123(1 Suppl):89S-96S. [Medline].
• Tang AW, Moss HA, Robertson RJ. The solitary pulmonary nodule. Eur J Radiol. Jan 2003;45(1):69-77. [Medline].
• Yi CA, Lee KS, Kim BT. Tissue characterization of solitary pulmonary nodule: comparative study between helical dynamic CT and integrated PET/CT. J Nucl Med. Mar 2006;47(3):443-50.

Article Last Updated: Jun 14, 2006