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Solitary Pulmonary Nodule

By

Rebecca Dezube

, MD, MHS, Johns Hopkins University

Last full review/revision Feb 2020| Content last modified Feb 2020
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Topic Resources

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. (Evaluation of a mediastinal mass is discussed elsewhere.)

Solitary pulmonary nodules are most often detected incidentally when a CT or chest x-ray is taken for other reasons, or during lung cancer screening. 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 Some Causes of a Solitary Pulmonary Nodule). Of these, the most common vary by age and risk factors, but typically include

  • Granulomas

  • Pneumonia

  • Bronchogenic cysts

Table
icon

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

Rheumatoid nodules

Benign tumors

Fibroma

Hamartoma

Lipoma

Granulomatous infection

Atypical mycobacterial infection

Tuberculosis (TB)

Infection

Bacterial abscess

Dirofilariasis (dog heartworm infection)

Echinococcus cyst

Pneumocystis jirovecii

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.

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, 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 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: Estimating the Probability of Cancer in a 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 years 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 months, 6 months, and then yearly for 2 years.

  • 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, granulomatosis with polyangiitis, 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
icon

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 (years)

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 years (average number of cigarettes/day)

1–9

0.3

10–20

1.0†

21–40

2.0

41

3.9

Quit smoking (years)

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-year-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 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. However, both false-positive and false-negative results occur. 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.

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 using serial CT scanning is reasonable. The timing and duration of follow-up CT scans are based mostly on the size, number, and morphology of the nodule (see link the 2017 Fleischer Society Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images). 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, 2017. https://doi.org/10.1148/radiol.2017161659

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