A solitary pulmonary nodule is a discrete lesion < 3 cm in diameter that is completely surrounded by lung parenchyma (ie, does not touch the hilum, mediastinum, or pleura) and is without associated atelectasis or pleural effusion.
A pulmonary nodule is a focal, distinct radiographic density < 3 cm in size and completely surrounded by lung tissue. In the United States, pulmonary nodules are incidentally detected in approximately 1.6 million patients annually (1). Evaluation of a mediastinal mass is discussed elsewhere.
Solitary pulmonary nodules are most often detected incidentally when a CT or chest radiograph is taken for other reasons, or during lung cancer screening. They appear on about 30% of chest CT scans (1). Nonpulmonary soft-tissue densities caused by nipple shadows, warts, cutaneous nodules, and bone abnormalities may often be confused for a nodule on chest radiograph.
General reference
1. Mazzone PJ, Lam L: Evaluating the Patient With a Pulmonary Nodule: A Review. JAMA 327(3):264–273, 2022. doi:10.1001/jama.2021.24287
Etiology of Solitary Pulmonary Nodule
Solitary pulmonary nodules have many causes (see table Some Causes of a Solitary Pulmonary Nodule). Although clinically the most important to exclude, it should be noted that the probability of malignancy is less than 1% for all nodules < 6 mm and 1 to 2% for nodules between 6 and 8 mm (1). Of these, the most common vary by age and risk factors, but typically include:
Granulomas
Pneumonia
Bronchogenic cysts
Some Causes of a Solitary Pulmonary Nodule
Cause | Examples |
|---|---|
Malignant causes* | |
Primary lung cancer | Adenocarcinoma Small cell carcinoma |
Metastatic cancer | Sarcoma |
Nonmalignant causes | |
Autoimmune disorders | |
Benign tumors | Fibroma Hamartoma Lipoma |
Granulomatous infection | Atypical mycobacterial infection Tuberculosis (TB) |
Infection | Bacterial abscess Dirofilariasis (dog heartworm infection) Echinococcus cyst Pneumocystis jirovecii infection |
Pulmonary vascular abnormalities | Cavernous angioma Hemangioma Pulmonary arteriovenous malformation Pulmonary telangiectasis |
Other | Bronchogenic cyst Hematoma Intrapulmonary lymph node Loculated fluid Mucoid impaction Rounded atelectasis |
* The likelihood of a malignant cause increases with age. | |
Etiology reference
1. Mazzone PJ, Lam L: Evaluating the Patient With a Pulmonary Nodule: A Review. JAMA 327(3):264–273, 2022. doi:10.1001/jama.2021.24287
Evaluation of Solitary Pulmonary Nodule
The primary goal of evaluation is to detect cancer and active infection. Several society guidelines have been developed for this purpose (1, 2, 3); recommendations also vary by geographical region (4, 5, 6).
History
History may reveal information that suggests malignant and nonmalignant causes of a solitary pulmonary nodule and includes:
Current or past cigarette smoking
History of cancer or an autoimmune disorder
Occupational risk factors for cancer (eg, exposure to asbestos, vinyl chloride, radon)
Travel to, or living in, areas with endemic mycosis or a high prevalence of tuberculosis (TB)
Risk factors for opportunistic infections (eg, HIV, immune deficiency)
Older age, cigarette smoking, and a personal history of cancer all increase the probability of cancer and are used along with the nodule diameter to estimate likelihood ratios for cancer.
Physical examination
A thorough physical examination may uncover findings that suggest an etiology (eg, a breast lump or skin lesion suggestive of cancer) for a pulmonary nodule but cannot definitely establish the cause.
Testing
The goal of initial testing is to estimate the malignant potential of the solitary pulmonary nodule. The first step is a review of plain radiographs and then usually CT.
Radiographic characteristics help define the malignant potential of a solitary pulmonary nodule:
Growth rate is determined by comparison with previous chest radiograph or CT, if available. A lesion that has not enlarged in ≥ 2 years suggests a benign etiology. Tumors that have volume doubling times from 21 to 400 days are likely to be malignant.
Calcification suggests nonmalignant disease, particularly if it is central (tuberculoma, histoplasmoma), concentric (healed histoplasmosis), or in a popcorn configuration (hamartoma).
Margins that are spiculated or irregular (scalloped) are more indicative of cancer.
Diameter< 1.5 cm strongly suggests a benign etiology; diameter > 5.3 cm strongly suggests cancer. However, nonmalignant exceptions include lung abscess, granulomatosis with polyangiitis, and hydatid cyst.
Location in the upper lobe carries a higher risk of malignancy.
These characteristics are sometimes evident on the original plain film but usually require CT. CT can also distinguish pulmonary from pleural radiopacities. CT has a sensitivity of 70% and a specificity of 60% for detecting cancer.
The mainstay of diagnosis of solitary pulmonary nodules is interval imaging. Specific imaging recommendations depend on the size of the nodule and whether the nodule is ground-glass, semi-solid, or solid, and individual risk factors (history of heavy smoking, exposure to asbestos, family history of lung cancer, older age [1]).
Positron emission tomography (PET) imaging can help differentiate cancerous and benign nodules. PET is most often used to image nodules whose probability of being cancerous is intermediate or high. It has a sensitivity > 90% and a specificity of about 78% for detecting cancer. PET activity is quantified by the standardized uptake value (SUV) of (18)F-2-deoxy-2-fluoro-D-glucose (FDG). SUV > 2.5 suggests cancer, while nodules with SUV < 2.5 are more likely to be benign. False-negative results are more likely if nodules are < 8 mm. False-negative PET scans can result from metabolically inactive tumors, and false-positive results can occur in various infectious and inflammatory conditions.
Cultures may be useful when historical information suggests an infectious cause (eg, TB, coccidioidomycosis) as a possible diagnosis.
Invasive testing options include:
CT- or ultrasound-guided transthoracic needle aspiration
Flexible bronchoscopy
Surgical biopsy
Although cancers can be diagnosed by biopsy, definitive treatment is resection, and so patients with a high likelihood of cancer with a resectable lesion should proceed to surgical resection. However, bronchoscopic endobronchial ultrasound-guided mediastinal lymph node biopsy is being used increasingly and is recommended by some experts as a less invasive way to diagnose and stage lung cancers before nodules are surgically resected.
Transthoracic needle aspiration is best for peripheral lesions and is particularly useful if infectious etiologies are strongly considered because using the transthoracic approach, as opposed to bronchoscopy, avoids the possibility of contamination of the specimen with upper airway organisms. The main disadvantage of transthoracic needle aspiration is the risk of pneumothorax, which is about 10%.
Flexible bronchoscopy allows for endobronchial washing, brushing, needle aspiration, and transbronchial biopsy. Yield is higher for larger, more centrally located lesions, but very experienced operators using specially designed thin scopes can successfully biopsy peripheral lesions that are < 1 cm in diameter.
In cases in which nodules are not accessible from these less invasive approaches, open surgical biopsy is necessary.
Evaluation references
1. Christensen J, Prosper AE, Wu CC, et al: ACR Lung-RADS v2022: Assessment Categories and Management Recommendations. J Am Coll Radiol 21(3):473–488., 2024 doi:10.1016/j.jacr.2023.09.009
2. Gould MK, Donington J, Lynch WR, et al: Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143(5 Suppl):e93S–e120S, 2013. doi:10.1378/chest.12-2351
3. MacMahon H, Naidich DP, Goo JM, et al: Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology 284(1):228–243, 2017. doi:10.1148/radiol.2017161659
4. Bai C, Choi CM, Chu CM, et al: Evaluation of Pulmonary Nodules: Clinical Practice Consensus Guidelines for Asia. Chest 150(4):877–893, 2016. doi:10.1016/j.chest.2016.02.650
5. Callister ME, Baldwin DR, Akram AR, et al: British Thoracic Society guidelines for the investigation and management of pulmonary nodules. Thorax 70 Suppl 2:ii1–ii54, 2015. doi:10.1136/thoraxjnl-2015-207168
6. Lam S, Bryant H, Donahoe L, et al: Management of screen-detected lung nodules: A Canadian partnership against cancer guidance document. Canadian Journal of Respiratory, Critical Care, and Sleep Medicine 4(4):236–265, 2020. doi:10.1080/24745332.2020.1819175
Treatment of Solitary Pulmonary Nodule
Sometimes surgery
Sometimes observation
If the suspicion of cancer is very low, the lesions are very small (< 1 cm), or the patient refuses or is not a candidate for surgical intervention, observation using serial CT scanning is reasonable. The timing and duration of follow-up CT scans are based mostly on the size and morphology of the nodule (1). Other factors that influence monitoring frequency include the location of the nodule, presence of emphysema or fibrosis on CT scan, age, sex, race, family history, and history of tobacco use (1).
When cancer is the most likely cause or when nonmalignant causes are unlikely, patients should undergo resection unless surgery is contraindicated due to poor pulmonary function, comorbidities, or withholding of consent.
Treatment reference
1. MacMahon H, Naidich DP, Goo JM, et al: Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology 284(1):228–243, 2017. doi:10.1148/radiol.2017161659
