A solitary pulmonary nodule is defined as 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 (for evaluation of a mediastinal mass, see Mediastinal and Pleural Disorders: Mediastinal Masses).

Solitary pulmonary nodules are most often detected incidentally when a chest x-ray is taken for other reasons. Nonpulmonary soft-tissue densities caused by nipple shadows, warts, cutaneous nodules, and bone abnormalities are often confused for a nodule on chest x-ray.

Etiology

Although cancer is usually the primary concern, solitary pulmonary nodules have many causes (see Table 6: Symptoms of Pulmonary Disorders: Some Causes of a Solitary Pulmonary Nodule). Of these, the most common vary by age and risk factors, but typically include

Table 6
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Some Causes of a Solitary Pulmonary Nodule Cause Examples Malignant causes* Primary lung cancer Adenocarcinoma Small cell carcinoma Metastatic cancer Breast cancer Melanoma Colon carcinoma Head and neck cancer Renal carcinoma Testicular carcinoma Sarcoma Nonmalignant causes Autoimmune disorders Rheumatoid nodules Wegener's granulomatosis Benign tumors Fibroma Hamartoma Lipoma Granulomatous infection Atypical mycobacterial infection Blastomycosis Coccidioidomycosis Cryptococcosis Histoplasmosis TB Infection Ascariasis Aspergilloma Bacterial abscess Dirofilariasis (dog heartworm infection) Echinococcus cyst Pneumocystis jirovecii Pulmonary vascular abnormalities Cavernous angioma Hemangioma Pulmonary arteriovenous malformation Pulmonary telangiectasis Other Amyloidosis Bronchogenic cyst Hematoma Intrapulmonary lymph node Loculated fluid Mucoid impaction Rounded atelectasis *The likelihood of a malignant cause increases with age.

• Granulomas
• Pneumonia
• Bronchogenic cysts

Evaluation

The primary goal of evaluation is to detect cancer and active infection.

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 areas with endemic mycosis or high prevalence of TB
• Risk factors for opportunistic infections (eg, HIV, immune deficiency)

Older age, cigarette smoking, and history of cancer all increase the probability of cancer and are used along with the nodule diameter to estimate likelihood ratios for cancer (see Table 7: Symptoms of Pulmonary Disorders: Solitary Pulmonary Nodule).

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 x-rays 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 x-ray or CT, if available. A lesion that has not enlarged in ≥ 2 yr suggests a benign etiology. Tumors that have volume doubling times from 21 to 400 days are likely to be malignant. Small nodules (< 1 cm) should be monitored at 3 mo, 6 mo, and then yearly for 2 yr.
• Calcification suggests benign 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, Wegener's granulomatosis, and hydatid cyst.

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.

Table 7
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Estimating the Probability of Cancer in a Solitary Pulmonary Nodule I. Establish likelihood ratios (LRs)* for cancer with the following table: Finding LR for Cancer Diameter of nodule (cm) < 1.5 0.1 1.5–2.2 0.5† 2.3–3.2 1.7 3.3–4.2 4.3 4.3–5.2 6.6 5.3–6.0 29.4 Patient's age (yr) ≤ 35 0.1 36–44 0.3 45–49 0.7 50–59 1.5 60–69 2.1† 70–83 5.7 Smoking history Never smoked 0.15 Pipe or cigar only 0.3 Ex-cigarette smoker 1.5 Current smoker or one who quit within past 9 yr (average number of cigarettes/day) 1–9 0.3 10–20 1.0† 21–40 2.0 ≥ 41 3.9 Quit smoking (yr) ≤ 3 1.4 4–6 1.0 7–12 0.5 ≥ 13 0.1 Overall prevalence Clinical settings 0.7† Community surveys 0.1 II. Multiply the LRs for nodule diameter, patient's age, smoking history, and cancer prevalence to obtain an estimate of the odds of cancer in a solitary pulmonary nodule (OddsCA): OddsCA = LR Size × LR Age × LR Smoking × LR Prev In the example: OddsCA = (1.5 × 2.1 × 1.0 × 0.7) = 2.21:1 III. Convert the odds into a probability of cancer: Probability of cancer (PCA) = OddsCA / (1 + OddsCA) × 100 = % In the example: PCA (as %) = 2.21/(1 + 2.21) × 100 = 69% *The LR is a measure of how predictive a finding is of disease and is defined as the probability of the finding being present in a patient with disease divided by the probability of the finding being present in a patient without disease; ie, it is the ratio of true positives to false positives or of sensitivity to 1– specificity. †The example is a 65-yr-old who smokes 20 cigarettes/day and has a 2.0-cm nodule. Adapted from Cummings SR, Lillington GA, Richard RJ: Estimating the probability of malignancy in solitary pulmonary nodules. A Bayesian approach. The American Review of Respiratory Disease 134 (3):449–452, 1986. Estimating the Probability of Cancer in a Solitary Pulmonary Nodule I. Establish likelihood ratios (LRs)* for cancer with the following table: Finding LR for Cancer Diameter of nodule (cm) < 1.5 0.1 1.5–2.2 0.5† 2.3–3.2 1.7 3.3–4.2 4.3 4.3–5.2 6.6 5.3–6.0 29.4 Patient's age (yr) ≤ 35 0.1 36–44 0.3 45–49 0.7 50–59 1.5 60–69 2.1† 70–83 5.7 Smoking history Never smoked 0.15 Pipe or cigar only 0.3 Ex-cigarette smoker 1.5 Current smoker or one who quit within past 9 yr (average number of cigarettes/day) 1–9 0.3 10–20 1.0† 21–40 2.0 ≥ 41 3.9 Quit smoking (yr) ≤ 3 1.4 4–6 1.0 7–12 0.5 ≥ 13 0.1 Overall prevalence Clinical settings 0.7† Community surveys 0.1 II. Multiply the LRs for nodule diameter, patient's age, smoking history, and cancer prevalence to obtain an estimate of the odds of cancer in a solitary pulmonary nodule (OddsCA): OddsCA = LR Size × LR Age × LR Smoking × LR Prev In the example: OddsCA = (1.5 × 2.1 × 1.0 × 0.7) = 2.21:1 III. Convert the odds into a probability of cancer: Probability of cancer (PCA) = OddsCA / (1 + OddsCA) × 100 = % In the example: PCA (as %) = 2.21/(1 + 2.21) × 100 = 69% *The LR is a measure of how predictive a finding is of disease and is defined as the probability of the finding being present in a patient with disease divided by the probability of the finding being present in a patient without disease; ie, it is the ratio of true positives to false positives or of sensitivity to 1– specificity. †The example is a 65-yr-old who smokes 20 cigarettes/day and has a 2.0-cm nodule. Adapted from Cummings SR, Lillington GA, Richard RJ: Estimating the probability of malignancy in solitary pulmonary nodules. A Bayesian approach. The American Review of Respiratory Disease 134 (3):449–452, 1986.

PET has an uncertain role in evaluation. It has a sensitivity > 90% and a specificity of about 78% for detecting cancer, but it is relatively new, and its role in evaluating pulmonary nodules is still being developed. 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, fiberoptic bronchoscopy, and 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%. Fiberoptic 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.

Treatment

• 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 is reasonable. Monitoring with follow-up at 3 mo, 6 mo, and then yearly for 2 yr is recommended. If the lesion has not grown for > 2 yr, it is likely benign.

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.

Last full review/revision July 2012 by Noah Lechtzin, MD, MHS