eMedicine Specialties > Pulmonology > Lung Tumors

Solitary Pulmonary Nodule

Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Asif Alavi, MD, Resident Physician, Department of Internal Medicine, University of California, Los Angeles, David Geffen School of Medicine, Olive View Medical Center; Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital; Sri R Navaratnam, MBBS, PhD, FRCPC, Assistant Professor, Department of Internal Medicine, Section of Hematology/Oncology, University of Manitoba; Consulting Medical Oncologist, Department of Hematology/Oncology, Cancer Care Manitoba

Updated: Sep 11, 2009

Introduction

Background

A solitary pulmonary nodule is defined as a discrete, well-marginated, rounded opacity less than or equal to 3 cm in diameter that is completely surrounded by lung parenchyma, does not touch the hilum or mediastinum, and is without associated atelectasis or pleural effusion.

Patients with solitary pulmonary nodules are usually asymptomatic; however, solitary pulmonary nodules 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?

Pathophysiology

A solitary pulmonary nodule 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. Lesions larger than 3 cm are considered masses and are treated as malignancies until proven otherwise.

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.

A solitary pulmonary nodule may be secondary to a wide differential of causes. However, greater than 95% are malignancies (most likely primary), granulomas (most likely infectious), or benign tumors (most likely hamartoma).

Frequency

United States

Solitary pulmonary nodules are one of the most common thoracic radiographic abnormalities. Approximately 150,000 cases are detected each year as an incidental finding, either on chest radiographs or thoracic CT scans.^{[1 ]}In lung cancer screening studies that enrolled people at high risk for lung cancer, the prevalence of solitary pulmonary nodules ranged from 8-51%.^{[2 ]}
 
Approximately 40-50% of solitary pulmonary nodules are malignant. Gould et al reported after a review of the literature that most of these are adenocarcinoma (47%), followed by squamous cell carcinoma (22%); small cell lung cancer makes up only 4% of malignant solitary pulmonary nodules.^{[3 ]}

Mortality/Morbidity

Most solitary pulmonary nodules are benign, but they may represent an early stage of lung cancer. Although lung cancer survival rates remain dismally low at 14% at 5 years, early lung cancer (ie, diagnosed when the primary tumor has a diameter <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 solitary pulmonary nodule 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

History

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

• History of malignancy
• History of smoking
• Occupational risk factors for lung cancer: Exposure to asbestos, radon, nickel, chromium, vinyl chloride, and polycyclic hydrocarbons can lead to the development of a solitary pulmonary nodule.
• 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 solitary pulmonary nodule.
• History of TB or pulmonary mycosis

Causes

• Neoplastic (malignant or benign)
  • Bronchogenic carcinoma
    • Adenocarcinoma (including bronchoalveolar carcinoma)
    • Squamous cell carcinoma
    • Large cell lung carcinoma
    • Small cell lung cancer
  • 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
  • Bronchogenic cyst
• Miscellaneous
  • Pulmonary infarct
  • Round atelectasis
  • Mucoid impaction
  • Progressive massive fibrosis

Differential Diagnoses

Workup

Laboratory 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 a 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 and computed tomography

Because solitary pulmonary nodules are first detected on chest radiographs, the initial distinction is whether the nodule is pulmonary or extrapulmonary in nature. Findings from a lateral chest radiography, fluoroscopy, or CT scanning may help confirm the location of the nodule. Although nodules of 5 mm in diameter are occasionally visualized on chest radiographs, solitary pulmonary nodules are quite often 8-10 mm in diameter.

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.

A left upper lobe solitary pulmonary nodule. The differential diagnosis is large, but CT scan findings help narrow the differentials and establish the diagnosis.

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; thus, these measurements are no longer routinely used.

With regard to dynamic contrast enhancement, 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. A multicenter study, using a cutoff value of 15 HU, found a sensitivity and specificity of 98% and 58%.^{[5 ]}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.

• Size: Although a well-defined nodule of smaller size that is clearly visible on chest radiographs may be calcified and benign, small lesions may very well be early-stage bronchogenic carcinoma. A lesion greater 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. Midthun et al indicated that the likelihood of malignancy was 50% in nodules greater than 20 mm and 18% for those 8-20 mm in diameter. With lesions smaller than 8 mm, a sharp decline is noted, with nodules of 4-7 mm having a likelihood of malignancy of only 0.9% and those less that 3 mm only 0.2%.^{[6 ]}
• 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. Important exceptions are bronchoalveolar carcinoma, which may require more than 2 years to double in size, and metastases from specific tumors (eg, osteosarcoma, choriosarcoma), which grow rapidly.^{[7 ]}
  • In general, 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.

Close-up view of a right lower lobe nodule demonstrating central calcification. The most likely diagnosis is histoplasmosis.

A "popcorn" calcification in the left lung nodule indicates a benign lesion or hamartoma. No further tests or observations are needed for this patient.

Right upper lobe nodule shows peripheral calcification and high Hounsfield unit enhancement, suggesting that the lesion is a calcified benign pulmonary nodule.

• Border characteristics
  • 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.
  • Cavitation with a thin, smooth wall may indicate lung abscess or a benign lesion, whereas thick-walled cavitations imply an underlying malignant neoplasm.

Left upper lobe cavitating solitary nodule eventually identified as active pulmonary tuberculosis from percutaneous needle biopsy findings.

Cavitating right lower lobe nodule later confirmed to be primary pulmonary lymphoma. Calcium deposits may also be present in the lesion.

• The 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.
• Internal characteristics: Several characteristics within the nodule itself can indicate a specific cause.
  • Demonstration of fat within the lesion is specific for a hamartoma, a benign lesion.

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.

• Ground-glass opacities may represent a benign lesion, such as atypical adenomatous hyperplasia, or malignancy, such as bronchoalveolar carcinoma.^{[3 ]}Importantly, malignant ground-glass opacities often grow slower and may require longer follow up.^{[2 ]}
• The presence of air bronchograms within the solitary pulmonary nodule 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.

Whether positron-emission tomography (PET) scanning will be useful depends on (1) the clinical pretest probability of malignancy, (2) nodule morphology, (3) the size and position of the nodule, and (4) the scanning facility available.

Because malignant nodules have increased glucose metabolism compared with benign lesions and healthy lungs, enhancement of the lesion makes it likely to be malignant. Injection of analogue 18-F-2 fluorodeoxyglucose (FDG) 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 the 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.

Several studies have reported the sensitivity, specificity, and accuracy of FDG-PET scanning to be greater than 90%, 75%, and 90%, respectively,^{[8 ]}including a meta-analysis of 40 studies evaluating 1474 focal pulmonary lesions of any size.^{[9 ]}FDG-PET scanning is an accurate and noninvasive imaging test for the diagnosis of pulmonary nodules and larger masses. However, not much data are available for nodules smaller than 1 cm in diameter.

One study compared the diagnostic accuracy of helical dynamic CT (HDCT) scanning and integrated PET/CT scanning for pulmonary nodule characterization. The sensitivity, specificity, and accuracy for malignancy with HDCT scanning were 81% (64 of 79 nodules), 93% (37 of 40 nodules), and 85% (101 of 119 nodules), respectively, whereas the values for integrated PET/CT scanning were 96% (76 of 79 nodules), 88% (35 of 40 nodules), and 93% (111 of 119 nodules), respectively.^{[10 ]}Integrated PET/CT scanning is more sensitive and accurate than HDCT scanning for malignant nodule diagnosis, making it the first-line evaluation tool for solitary pulmonary nodules. Because of the high specificity and acceptable sensitivity and accuracy of HDCT scanning, it may be a reasonable alternative if PET/CT scanning is unavailable.

Single-photon emission computed tomography (SPECT) scanning is less expensive than PET scanning, but both modalities 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 Tc 99m depreotide in differentiating benign solitary pulmonary nodules from malignant solitary pulmonary nodules.^{[11 ]}They also compared the diagnostic accuracy of^99m Tc with FDG-PET scanning in a prospective, multicenter trial. SPECT scanning with^99m Tc depreotide revealed a sensitivity, specificity, and diagnostic accuracy of 89%, 67%, and 81%, respectively. Furthermore, in patients who underwent both^99m Tc depreotide SPECT imaging and FDG-PET imaging, the sensitivity, specificity, and diagnostic accuracy were identical for both modalities.

Procedures

Biopsy

Biopsy of solitary pulmonary nodule 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. Fluoroscopy or endobronchial ultrasound can be used to localize the lesions during TBNA to increase the diagnostic yield to 70% or more.^{[12,13 ]}
• 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 (approximately 70% accuracy); therefore, most benign lesions are characterized as nondiagnostic following TTNA. The rate of pneumothorax following TTNA is approximately 25%, with approximately 7% requiring chest intubation.^{[14 ]}

Treatment

Medical Care

Lesions that have typical benign features, such as lack of change over 2 years or a benign pattern of calcification, especially in low-risk patients, do not require further workup. On the other hand, lesions that are strongly suggestive of malignancy (eg, >3 cm diameter) or those with documented growth should be referred for surgical resection.^{[15 ]}Management decisions for lesions with intermediate probability (which are most lesions) are more complex. Although management varies amongst individual institutions and practitioners, several guidelines have been published.

In 2005, the Fleischner Society published guidelines^{[16 ]}for follow-up imaging of solitary pulmonary nodules (SPNs). They specified different strategies based on patient risk factors and the size of the nodule

• Low-risk patients
  • Less than or equal to 4 mm - No further investigation
  • 4-6 mm - CT scanning at 12 months
  • 6-8 mm - CT scanning at 6-12 months and 18-24 months
  • Greater than 8 mm - CT scanning at 3, 9, and 24 months; contrast-enhanced CT scanning; positron-emission tomography (PET) scanning; and/or biopsy
• High-risk patients
  • Less than or equal to 4 mm - CT scanning at 12 months
  • 4-6 mm - CT scanning at 6-12 months and 18-24 months
  • 6-8 mm - CT scanning at 3–6 months, 9–12 months, and 24 months
  • Greater than 8 mm - Same as low-risk patients

• Carefully calculate pretest probability for malignancy, either through experienced clinical judgment or through the use of a validated model, such as Bayesian analysis.^{[17 ]}
• Previous chest radiographs should be reviewed to determine if the lesion has been stable over 2 years. If so, no further follow up is necessary, with the exception of pure ground-glass lesions on CT scans, which can be slower growing.
• For lesions with a benign pattern of calcification, further testing is not necessary.
• Management of indeterminate lesions greater than 8-10 mm depends on clinical probability of malignancy, as follows:
  • Low probability - Serial CT scanning at 3, 6, 12, and 24 months
  • Intermediate probability - 18-Fluorodeoxyglucose (FDG) PET scanning, contrast-enhanced CT scanning, transthoracic needle aspiration (TTNA), and/or transbronchial needle aspiration (TBNA) (Thoracoscopic diagnosis is recommended for patients who wish to have a surgical diagnosis if the lesion is in the peripheral third of the lung.)
  • High probability - Surgical resection
  • Subcentimeter lesions - Same as Fleischner Society, as listed above
  • Any unequivocal growth noted during follow up - Definitive tissue diagnosis needed

Surgical Care

When a lesion is likely to be malignant, surgical resection—not TTNA or observation—is often used.

• The 2007 ACCP guidelines recommend that patients who have indeterminate lung nodules with a high probability of malignancy undergo thoracoscopic wedge resections if the lesion is in the peripheral third of the lung. This is because of the relatively low morbidity and mortality associated with the procedure compared with thoracotomy.^{[18 ]}If frozen sections show evidence of malignancy, anatomic resection with mediastinal lymph node sampling or dissection may be performed.
• Localization using methylene blue injection or 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.^{[19 ]}

Follow-up

Deterrence/Prevention

Avoiding certain exposures may help prevent certain causes of solitary pulmonary nodule formation. Possible avoidable exposures include the following:

• Risk factors for malignancy
  • Smoking
  • Occupational exposures (eg, asbestos, radon, nickel, chromium, vinyl chloride, polycyclic hydrocarbons)
• Travel to areas endemic for mycosis (eg, histoplasmosis, coccidioidomycosis, blastomycosis) or to areas with a high prevalence of tuberculosis

Complications

Most solitary pulmonary nodules 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 solitary pulmonary nodule is prompt diagnosis and management.

Miscellaneous

Medicolegal 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 scanning, positron-emission tomography [PET] scanning, single-photon emission computed tomography [SPECT] scanning), and invasive diagnostic procedures.

Because determining the retest probability of malignancy is essential in guiding the management of solitary pulmonary nodules, estimating the probability of benignity using a validated quantitative model might be an effective strategy. Bayesian analysis combines the radiologic features of a nodule and the clinical findings of an individual patient to estimate the probability of malignancy.

• The radiographic features of solitary pulmonary nodules 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.^{[21 ]}

Because the evidence is not definitive for many of the management guidelines, clinicians should discuss with patients the risks and benefits of alternative management options and should elicit patient preferences. 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. Finally, because invasive procedures such as transthoracic needle aspiration (TTNA), transbronchial needle aspiration (TBNA), and video-assisted thoracoscopic surgery (VATS) may be associated with risks and complications, informed consent must be obtained.

Multimedia

Media file 1: Right upper lobe nodule shows peripheral calcification and high Hounsfield unit enhancement, suggesting that the lesion is a calcified benign pulmonary nodule.

Media file 2: 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.

Media file 3: Mediastinal windows of the patient in Media File 2.

Media file 4: Right lower lobe nodule demonstrating central calcification. The most likely diagnosis is histoplasmosis.

Media file 5: Close-up view of a right lower lobe nodule demonstrating central calcification. The most likely diagnosis is histoplasmosis.

Media file 6: Left upper lobe cavitating solitary nodule eventually identified as active pulmonary tuberculosis from percutaneous needle biopsy findings.

Media file 7: A left upper lobe nodule with central lucency and poorly circumscribed margins was diagnosed as actinomycosis based on needle biopsy findings.

Media file 8: CT scan of the patient presented in Media File 7. After needle biopsy, the presence of classic sulfur granules confirmed actinomycosis.

Media file 9: A right lower lobe solitary pulmonary nodule later identified to be a hamartoma.

Media file 10: Wedge-shaped peripheral (pleural based) density observed secondary to pulmonary infarction (pulmonary embolism). This is termed the Westermark sign.

Media file 11: Left upper lobe 1.5-cm nodule shows negative CT scan numbers, suggesting fat in the lesion consistent with hamartoma.

Media file 12: A left upper lobe solitary pulmonary nodule. The differential diagnosis is large, but CT scan findings help narrow the differentials and establish the diagnosis.

Media file 13: Cavitating right lower lobe nodule later confirmed to be primary pulmonary lymphoma. Calcium deposits may also be present in the lesion.

Media file 14: This left lower lobe carcinoid tumor was quite bloody after a percutaneous needle biopsy was performed.

Media file 15: A lateral radiograph of the case in Media File 14.

Media file 16: CT scan of the patient in Media File 14 shows a well-circumscribed lesion.

Media file 17: A "popcorn" calcification in the left lung nodule indicates a benign lesion or hamartoma. No further tests or observations are needed for this patient.

Media file 18: 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.

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.

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.

References

1. Lillington GA. Management of solitary pulmonary nodules. Dis Mon. May 1991;37(5):271-318. [Medline].

2. Wahidi MM, Govert JA, Goudar RK, Gould MK, McCrory DC. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. Sep 2007;132(3 Suppl):94S-107S. [Medline].

3. [Guideline] Gould MK, Fletcher J, Iannettoni MD, et al. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. Sep 2007;132(3 Suppl):108S-130S. [Medline]. [Full Text].

4. Cardinale L, Ardissone F, Novello S, et al. The pulmonary nodule: clinical and radiological characteristics affecting a diagnosis of malignancy. Radiol Med. May 29 2009;[Medline].

5. Swensen SJ, Viggiano RW, Midthun DE, et al. Lung nodule enhancement at CT: multicenter study. Radiology. Jan 2000;214(1):73-80. [Medline]. [Full Text].

6. Midthun DE, Swensen SJ, Jett JR, Hartman TE. Evaluation of nodules detected by screening for lung cancer with low dose spiral computed tomography. Lung Cancer. Aug 2003;41 (suppl 2):S40.

7. Ost D, Fein AM, Feinsilver SH. Clinical practice. The solitary pulmonary nodule. N Engl J Med. Jun 19 2003;348(25):2535-42. [Medline]. [Full Text].

8. Behzadi A, Ung Y, Lowe V, Deschamps C. The role of positron emission tomography in the management of non-small cell lung cancer. Can J Surg. Jun 2009;52(3):235-42. [Medline].

9. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. 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].

10. Yi CA, Lee KS, Kim BT, Choi JY, Kwon OJ, Kim H. 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. [Medline].

11. Naalsund A, Maublant J. The solitary pulmonary nodule--is it malignant or benign? Diagnostic performance of Tc-depreotide SPECT. Respiration. 2006;73(5):634-41. [Medline].

12. Herth FJ, Eberhardt R, Becker HD, Ernst A. Endobronchial ultrasound-guided transbronchial lung biopsy in fluoroscopically invisible solitary pulmonary nodules: a prospective trial. Chest. Jan 2006;129(1):147-50. [Medline]. [Full Text].

13. Herth FJ, Ernst A, Becker HD. Endobronchial ultrasound-guided transbronchial lung biopsy in solitary pulmonary nodules and peripheral lesions. Eur Respir J. Oct 2002;20(4):972-4. [Medline]. [Full Text].

14. 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].

15. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest. Jan 2003;123(1 Suppl):89S-96S. [Medline]. [Full Text].

16. [Guideline] MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. Nov 2005;237(2):395-400. [Medline]. [Full Text].

17. Gurney JW. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part I. Theory. Radiology. Feb 1993;186(2):405-13. [Medline]. [Full Text].

18. Watanabe A, Koyanagi T, Obama T, et al. Assessment of node dissection for clinical stage I primary lung cancer by VATS. Eur J Cardiothorac Surg. May 2005;27(5):745-52. [Medline]. [Full Text].

19. Shennib H. Intraoperative localization techniques for pulmonary nodules. Ann Thorac Surg. Sep 1993;56(3):745-8. [Medline].

20. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. Sep 1995;60(3):615-22; discussion 622-3. [Medline].

21. 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].

22. 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.

23. Chung T. Fine needle aspiration of the solitary pulmonary nodule. Semin Thorac Cardiovasc Surg. Jul 2002;14(3):275-80. [Medline].

24. Decamp MM Jr. The solitary pulmonary nodule: aggressive excisional strategy. Semin Thorac Cardiovasc Surg. Jul 2002;14(3):292-6. [Medline].

25. 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].

26. 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].

27. Ginsberg RJ. The solitary pulmonary nodule: can we afford to watch and wait?. J Thorac Cardiovasc Surg. Jan 2003;125(1):25-6. [Medline].

28. 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].

29. Gould MK, Lillington GA. Strategy and cost in investigating solitary pulmonary nodules. Thorax. Aug 1998;53 Suppl 2:S32-7. [Medline].

30. Hartman TE. Radiologic evaluation of the solitary pulmonary nodule. Radiol Clin North Am. May 2005;43(3):459-65, vii. [Medline].

31. 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.

32. Jain P, Kathawalla SA, Arroliga AC. Managing solitary pulmonary nodules. Cleve Clin J Med. Jun 1998;65(6):315-26. [Medline].

33. Laurent F, Remy J. [Management strategy of pulmonary nodules]. J Radiol. Dec 2002;83(12 Pt 1):1815-21. [Medline].

34. Lillington GA. Management of solitary pulmonary nodules. How to decide when resection is required. Postgrad Med. Mar 1997;101(3):145-50. [Medline].

35. Lillington GA. Solitary pulmonary nodules: new wine in old bottles. Curr Opin Pulm Med. Jul 2001;7(4):242-6. [Medline].

36. Lillington GA, Caskey CI. Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med. Mar 1993;14(1):111-9. [Medline].

37. Moses DA, Ko JP. Multidetector CT of the solitary pulmonary nodule. Semin Roentgenol. Apr 2005;40(2):109-25. [Medline].

38. 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].

39. Pepe G, Rossetti C, Sironi S, Landoni C, Gianolli L, Pastorino U. 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. [Medline].

40. Plachcinska A, Mikolajczak R, Kozak J, Rzeszutek K, Kusmierek 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. [Medline].

41. Pogodina VV. Elizaveta Nilolaevna Levkovich-75th birthday. Acta Virol. Nov 1975;19(6):509. [Medline].

42. Schaefer JF, Schneider V, Vollmar J, Wehrmann M, Aebert H, Friedel G. Solitary pulmonary nodules: association between signal characteristics in dynamic contrast enhanced MRI and tumor angiogenesis. Lung Cancer. Jul 2006;53(1):39-49. [Medline].

43. 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.

44. Shaham D, Guralnik L. The solitary pulmonary nodule: radiologic considerations. Semin Ultrasound CT MR. Apr 2000;21(2):97-115. [Medline].

45. Siegelman SS, Zerhouni EA, Leo FP, Khouri NF, Stitik FP. CT of the solitary pulmonary nodule. AJR Am J Roentgenol. Jul 1980;135(1):1-13. [Medline].

46. Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. 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].

47. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest. Jan 2003;123(1 Suppl):89S-96S. [Medline].

48. Tang AW, Moss HA, Robertson RJ. The solitary pulmonary nodule. Eur J Radiol. Jan 2003;45(1):69-77. [Medline].

Keywords

solitary pulmonary nodule, SPN, early lung cancer, histoplasmosis, coccidioidomycosis, blastomycosis, pulmonary mycosis, tuberculosis, TB, bronchogenic carcinoma, nocardiosis, asbestos exposure, radon exposure, nickel exposure, chromium exposure, vinyl chloride exposure, polycyclic hydrocarbon exposure, chemical exposure, industrial exposure, bronchogenic cancer, bronchogenic malignancy, pulmonary mycosis, mycosis, lung nodule, malignant nodule, lung lesion, lung malignancy, neoplasm, primary neoplasm, lung neoplasm, granuloma, infectious granuloma, lung granuloma, benign lung lesion, hamartoma, lymphoma, carcinoid, fibroma, neurofibroma, blastoma, sarcoma, lung abscess, round pneumonia, hydatid cyst, rheumatoid arthritis, RA, Wegener granulomatosis, sarcoidosis, lipoid pneumonia, arteriovenous malformation, AVM, lung cyst, pulmonary infarct, round atelectasis, mucoid impaction, mucus impaction, progressive massive fibrosis

Contributor Information and Disclosures

Author

Nader Kamangar, MD, FACP, FCCP, FAASM, Associate Professor of Clinical Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Multi-campus Pulmonary and Critical Care Fellowship Program, University of California, Los Angeles, David Geffen School of Medicine; Medical Director, Hospitalist/Intensivist Program, Olive View-UCLA Medical Center; Associate Program Director, Combined Pulmonary and Critical Care Fellowship Program, Cedars-Sinai/Olive View-UCLA Medical Center/West Los Angeles Veterans Affairs Medical Center
Nader Kamangar, MD, FACP, FCCP, FAASM is a member of the following medical societies: American Academy of Sleep Medicine, American Association of Bronchology, American College of Chest Physicians, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, California Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Asif Alavi, MD, Resident Physician, Department of Internal Medicine, University of California, Los Angeles, David Geffen School of Medicine, Olive View Medical Center
Asif Alavi, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Sri R Navaratnam, MBBS, PhD, FRCPC, Assistant Professor, Department of Internal Medicine, Section of Hematology/Oncology, University of Manitoba; Consulting Medical Oncologist, Department of Hematology/Oncology, Cancer Care Manitoba
Disclosure: Nothing to disclose.

Medical Editor

Stephen P Peters, MD, PhD, Professor, Department of Medicine, Wake Forest University
Stephen P Peters, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, and Sigma Xi
Disclosure: See below for list of all activities None None

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

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