Pulmonary Nodules disease management


Pulmonary nodules are small, focal, radiographic opacities that may be solitary or multiple. A classic solitary pulmonary nodule (SPN) is a single, spherical, well-circumscribed, radiographic opacity measuring less than or equal to 30 mm in diameter and is surrounded completely by aerated lung.1 The SPN is a coined term that in the past described solitary nodules detected incidentally by chest radiography (CXR).2 Today, most nodules are detected by computed tomography (CT). The detailed CT images frequently identify more than one nodule, or enlarged lymph nodes. The term “solitary” should not be used in these circumstances. The term “coin lesion” should also be discouraged because nodules are spherical and not coin shaped.1 Indeterminate nodules are those that do not possess features clearly associated with a benign etiology, such as a benign pattern of calcification or stability on imaging for >2 years.1

Pulmonary lesions greater than 30 mm in diameter should be called masses rather than nodules. Masses have a high probability of being malignant.3 Subcentimeter nodules are less than 10 mm in diameter and are much less likely to be malignant.4 Subsolid nodules include pure ground-glass nodules (GGNs) and part-solid nodules.5 GGNs are defined as focal nodular areas of increased lung attenuation through which normal parenchyma structures such as airways, vessels, and interlobular septa can be visualized.5 Since first reported in 1996, it has become increasingly recognized that GGNs frequently represent adenocarcinomas or their precursors.

The widespread use of chest imaging has led to the detection of many pulmonary lesions. The American College of Chest Physicians (ACCP) does not recommend distinguishing between nodules detected by CXR versus CT. The goal in managing patients with pulmonary nodules is to distinguish between benign and malignant nodules, expediting diagnosis for malignant nodules while minimizing testing of those that are benign.

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The prevalence of pulmonary nodules varies significantly across studies. This variation stems from the inconsistency among studies in method, enrolled population, and reporting results.6 Most lung nodules are detected incidentally on CXR or CT scans obtained for other purposes. It is estimated that 0.09% to 0.2% of all CXR scans will incidentally detect pulmonary nodules.7 In CT angiograms obtained to diagnose pulmonary embolism, a study reports 13% of cases to have incidental findings of pulmonary nodules.8 In another cohort study, 31% of patients undergoing cardiac CT scans for coronary calcium scoring have incidental findings of pulmonary nodules.9

In lung cancer screening trials, 7% of CXR scans obtained from previously healthy individuals contain pulmonary nodules.6 CT scans to screen for lung cancer detect nodules in 8% to 51% of individuals screened.6 Given the findings from the National Lung Screening Trial, the use of low-dose CT scanning as a screening tool for lung cancer is expected to increase, leading to the discovery of many pulmonary nodules.10

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Differential Diagnoses

The primary concern when evaluating someone with a pulmonary nodule is that it could represent bronchogenic carcinoma. The differential diagnosis of lung nodules includes many benign diseases. Benign etiologies of pulmonary nodules include healed or nonspecific granulomas and active granulomatous infections, which account for 25% and 15% of all benign causes, respectively.1 Active granulomatous infections include tuberculosis, coccidioidomycosis, histoplasmosis, cryptococcus, and aspergillosis. Hamartomas comprise an additional 15% of benign lesions.1 Other benign causes include nonspecific inflammation and fibrosis, lung abscesses, round atelectasis, bronchogenic cysts, healed pulmonary infarcts, focal hemorrhage, hemangiomas, and arteriovenous malformations.1

The prevalence of malignancy in patients with pulmonary nodules ranges from 1.1% to 12%.6 This rate depends on the nodule characteristics and the population at risk. Most malignant pulmonary nodules are adenocarcinoma (47%), squamous cell carcinoma (22%), solitary metastasis (8%), and small cell lung cancer (4%).1 Other less common causes of malignant lung nodules include: large cell carcinoma, carcinoid tumors, lymphomas, adenosquamous carcinoma, adenoid cystic carcinoma, and malignant teratomas (Table 1).1
Table 1: Differential Diagnosis for a Pulmonary Nodule6
Benign Malignant (1.1%-12%)
Nonspecific granuloma (15%-25%) Adenocarcinoma (47%)
Harmatoma (15%) Squamous cell carcinoma (22%)
Infectious granuloma (15%)


Metastatic (8%)

Small cell lung carcinoma (4%)
Others: lung abscess, round pneumonia, bronchogenic cysts, focal hemorrhage, hemangiomas, AVMs Others: large cell carcinoma, carcinoid tumors, lymphomas, malignant teratomas

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Estimating the Probability of Malignancy

Traditionally, established historical and radiographic criteria are used to estimate the probability that a pulmonary nodule is malignant. If this probability is quite low, observation is chosen as the course to follow. If this probability is quite high, immediate surgical resection is indicated. Most pulmonary nodules lie somewhere between these extremes and are said to be indeterminate, requiring further evaluation. Traditional nodule evaluation is most relevant for solid nodules 1 cm or larger in size. The evaluation of subcentimeter and semi-solid nodules has evolved more recently. In considering these issues, this chapter will review the established clinical and radiographic criteria used to estimate the probability of malignancy in solid pulmonary nodules, current invasive and noninvasive methods of evaluating them, their respective test characteristics, and how test results influence the probability of malignancy. Separately, we will discuss some of the unique considerations in the evaluation of subcentimeter and semi-solid nodules. Finally, management guidelines for pulmonary nodules will be summarized.