Solitary Lung Nodule or Mass

A pulmonary nodule is defined as any pulmonary lesion that is well-defined, discrete, approximately circular, and 3 cm or less in diameter. The term mass is used for lesions greater than 3 cm in diameter. The differential diagnosis of a nodule or mass detected on a radiograph or CT is very broad ( Table 4.1 ). However, more than 95% fall into one of three groups: malignant neoplasms (primary or metastatic), infectious granulomas (tuberculosis or endemic fungi), or less commonly, benign tumors (neoplastic or nonneoplastic). Approximately 40% of solitary lung nodules detected on a chest radiograph represent primary lung cancer.

TABLE 4.1
SOLITARY PULMONARY NODULE OR MASS: DIFFERENTIAL DIAGNOSIS
Etiology Features
CONGENITAL
Bronchogenic cyst Water density on CT (50%). Almost all have high signal intensity on T2-weighted MRI
Pulmonary arteriovenous malformation Round, oval, or slightly lobulated. CT shows a feeding artery and draining vein
INFECTIOUS/INFLAMMATORY
Tuberculosis Common. Mainly upper lobes. Frequently calcifies
Histoplasmosis Common in endemic areas. Frequently calcifies
Coccidioidomycosis Common in endemic areas. Frequently cavitates. Rarely calcifies
Echinococcus Water density on CT
Lung abscess Cavitation or low-attenuation center on CT
Focal (round) pneumonia Less common in adults than in children. Tends to have ill-defined margins
Granulomatosis with polyangiitis A solitary nodule is uncommon
Rheumatoid nodules Necrobiotic rheumatoid nodules most commonly multiple
Organizing pneumonia Tends to have ill-defined margins
Lipoid pneumonia Irregular margins. Foci of fat density on CT (80%)
Conglomerate fibrosis in sarcoidosis Uncommon. Typically bilateral, perihilar, and upper lobes. Air bronchograms
Conglomerate fibrosis in talcosis Intravenous drug user. Typically upper lobes. Characteristic high attenuation because of talc deposition
PNEUMOCONIOSIS
Progressive massive fibrosis in silicosis Typically perihilar, bilateral, and upper lobes. Other findings of silicosis
NEOPLASTIC
Pulmonary carcinoma Smooth, lobulated, or most commonly, spiculated margins
Carcinoid tumor Relatively uncommon. Usually smooth margins
Hamartoma Uncommon. Tends to have lobulated margins. Sixty percent have areas of fat density on CT. Popcorn calcification characteristic but uncommon
Metastasis Solitary metastasis uncommon except for sarcoma. Tends to have smooth margins
TRAUMATIC
Hematoma Uncommon. Smooth margins. Usually in a peripheral location. Slow but progressive decrease in size

Most of the nodules detected radiographically measure more than 1 cm in diameter. Noncalcified nodules less than 7 mm in diameter are seldom visible on radiographs. In contrast, nodules as small as 1 to 2 mm in diameter are readily seen on CT. More than 50% of smokers who undergo thin-section CT have small lung nodules, almost all of which measure less than 7 mm in diameter. The vast majority of these small nodules are benign.

The first step in assessing a lesion detected on a chest radiograph is to determine that it is indeed a lung nodule rather than a pleural or chest wall abnormality, such as a healing rib fracture, pleural neoplasm, or skin lesion projecting over the lung ( Fig. 4.1 ). The next step is to evaluate the imaging characteristics of the nodule to determine whether there are findings that favor a benign or a malignant lesion. After this, one must integrate the imaging characteristics with clinical findings such as patient age, risk factors such as cigarette smoking or a known primary extrathoracic neoplasm, recent travel history, and symptoms such as fever or hemoptysis. For example, a nodule in an adolescent patient is likely to be benign, regardless of its margin characteristics. A growing noncalcified nodule in an older smoking patient is likely to be malignant even though it has smooth borders. In the vast majority of cases, pulmonary metastases are multiple. However, single lung metastases may also occur, particularly with sarcomas and testicular tumors.

Fig. 4.1, Lung nodule or mass versus a pleural or chest wall nodule or mass. (A) Frontal chest radiograph shows a cavitary left lower lobe nodule. All the margins of the nodule are well seen, suggesting a lung origin. (B) Axial CT scan confirms the intraparenchymal location of the cavitary left lower lobe nodule in a man with lung cancer. (C) Frontal chest radiograph from a different patient with localized fibrous tumor of the pleura shows a nodular opacity with tapered margins that forms an obtuse angle with the chest wall. Note that the inferior margins of the nodule are well defined, indicative of contact with lung, whereas the upper and outer margins are poorly defined, indicative of contact with the pleura and chest wall. This is called the “incomplete border sign” and helps suggest a pleural or chest wall location of a lesion. (D) Axial CT image from the same patient as (C) confirms the pleural origin of the abnormality.

Advances in multidetector CT have improved nodule detection and characterization with thin-section imaging, acquisition within a single breath-hold, high-quality volumetric image data, as well as multiplanar and maximum intensity projection (MIP) reconstructions ( Fig. 4.2 ). Of note, multiplanar CT images should be fully used in assessing a nodule's shape and appearance because linear opacities, as seen with atelectasis or scar, may appear nodular in a single plane. In the vast majority of cases, no intravenous contrast material is necessary for nodule characterization.

Fig. 4.2, Value of a maximum intensity projection (MIP) reconstruction in the detection of a small lung nodule. Composite image with axial CT image (left image) and MIP reconstruction (right image) shows a small left lower lobe nodule (arrows), better visualized on the MIP reconstruction.

In evaluating lung nodules, it is useful to divide them into two categories: (1) those that are clearly benign, as determined by rigidly defined radiologic signs, and (2) those of indeterminate nature, which represent all other lesions. This allows one to distinguish benign from malignant nodules with a reasonable degree of confidence.

Location of the Lesion

An intrapulmonary nodule tends to form an acute angle with the contiguous pleura and to have well-defined margins when seen en face (see Fig. 4.1A and B ). A nodule originating within the pleural space, rib, or chest wall displaces the pleura and underlying lung inward (see Fig. 4.1C and D ). It therefore tends to have tapered margins and form an obtuse angle with the chest wall and to have one side demonstrating a well-defined margin and the opposite side a poorly defined margin when seen en face (incomplete border sign). Similar to all other radiologic signs, this sign is fallible. Occasionally, an extrapulmonary nodule relates to the lung at an acute angle and an intrapulmonary mass at an obtuse angle.

Imaging Characteristics of Lung Nodules

Distinction between benign and malignant lesions can often be established with a reasonable degree of confidence from the clinical and radiographic findings, although findings are seldom pathognomonic. The main diagnostic radiologic criteria are nodule size, change in size over time, attenuation (including presence of calcification or fat), margin characteristics, and 18 F-fluorodeoxyglucose (FDG) avidity.

Size

The prevalence of malignancy typically varies by size with less than 1% for nodules less than 5 mm, 0.5% to 28% for nodules 5 to 10 mm, and 64% to 82% for nodules greater than 20 mm. When interpreting these figures it is important to remember that the likelihood of carcinoma is influenced strongly by other factors such as age and smoking history.

Change in Size

Because uncontrolled growth is a characteristic feature of cancer, in the absence of an infectious or inflammatory process, an enlarging pulmonary nodule should be considered malignant until proven otherwise by tissue sampling. However, because some benign lesions such as hamartoma and histoplasmoma can enlarge and some adenocarcinomas can grow slowly, an increase in the size of a nodule, by itself, should not be the sole consideration governing the therapeutic approach. Traditionally, 2-year stability in size has been considered a reasonably reliable criterion of benignity; however, the validity of this statement has been questioned, particularly with respect to ground-glass or part-solid nodules, in which a slight change in size may be difficult to appreciate. Patients with ground-glass and part-solid nodules require longer monitoring as outlined by the Fleischner criteria ( Tables 4.2 and 4.3 ).

TABLE 4.2
FLESICHNER CRITERIA FOR SOLID NODULES
Modified from MacMahon H, Naiditch NP, Goo JM, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner Society 2017. Radiology. 2017;284:228-243.
SOLID NODULE
<6 mm <6 mm 6–8 mm 6–8 mm >8 mm
Low Risk High Risk Low Risk High Risk Any Risk
Solitary No follow-up 12-mo CT if suspicious a 6- to 12-mo CT, consider 18- to 24-mo CT if suspicious a Both 6- to 12-mo CT and 18- to 24-mo CT Consider CT, PET/CT, or tissue sampling at 3 mo
Multiple No follow-up 12-mo CT if suspicious b 3- to 6-mo CT, consider 18- to 24-mo CT if suspicious b Both 3- to 6-mo CT and 18- to 24-mo CT 3- to 6-mo CT; additional 18- to 24-mo CT if high risk or suspicious b

a Suspicious by morphology or with upper lobe location.

b Based on most suspicious nodule.

TABLE 4.3
FLEISCHNER CRITERIA FOR SUBSOLID (GROUND-GLASS AND PART-SOLID) NODULES
Modified from MacMahon H, Naiditch NP, Goo JM, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner Society 2017. Radiology. 2017;284:228–243.
SOLITARY SUBSOLID NODULE
<6 mm ≥6 mm
Initial follow-up: Additional follow-up if stable:
Ground-glass No follow-up 6- to 12-mo CT Biannual CT until 5 years
Part-solid No follow-up 3- to 6-mo CT Annual CT at least 5 years (Note: Solid component must remain <6 mm; persistent part-solid nodules with solid component measuring ≥6 mm should be considered highly suspicious for adenocarcinoma.)
MULTIPLE SUBSOLID NODULES
<6 mm ≥6 mm
Initial follow-up 3- to 6-mo CT 3- to 6-mo CT
Additional follow-up (if stable) Consider 24- and 48-mo CT Per most suspicious nodule

Use of the doubling time provides a more accurate assessment of the nature of a pulmonary nodule than a simple increase in size does. Doubling refers to volume, not diameter. Assuming a nodule to be spherical, its diameter must be multiplied by 1.25 to obtain the diameter of a sphere whose volume is double (e.g., the volume of a nodule 2 cm in diameter is doubled by the time that its diameter reaches 2.5 cm). A doubling of diameter represents an eightfold increase in volume. Measurement of doubling time requires at least two serial chest radiographs or CT scans showing a roughly spherical lesion whose diameter can be averaged from measurements in at least two planes. In a study of 218 pulmonary nodules (177 malignant and 41 benign), virtually all nodules whose doubling time was 7 days or less or 465 days or longer were benign. A pulmonary nodule whose rate of growth falls between these limits is often malignant. A pitfall to be aware of is indolent lung cancer (particularly adenocarcinoma), which may manifest as a ground-glass nodule gradually enlarging over 5 years or longer. For this reason, ground-glass nodules merit longer follow-up, per the Fleischner criteria (see Table 4.3 ). Perhaps the most useful application of the growth rate principle in assessing solitary nodules is in patients older than 40 years, in whom the incidence of malignancy increases markedly. In a study of individuals in this older age group, almost every solitary nodule whose doubling time was less than 37 days was benign.

Attenuation: Calcification

Benign patterns of calcification within a solitary pulmonary nodule are one of the most reliable signs that a lesion is benign. Four patterns of calcification are characteristically associated with benign lesions: diffuse, laminated, central, and popcorn ( Fig. 4.3 ). The diffuse ( Fig. 4.4 ) and laminated (synonym: concentric or laminar) types of calcification are virtually diagnostic of a granuloma, although this cannot be applied to pulmonary masses (>3 cm in size). A small central nidus of calcification is seen most commonly with granulomatous lesions (typically tuberculosis and histoplasmosis), although it also occurs in some hamartomas. Popcorn calcification is characteristic of hamartoma ( Fig. 4.5 ). By contrast, the presence of an eccentric calcification in a nodule or mass may represent incorporation of a calcified granuloma within the substance of a carcinoma.

Fig. 4.3, Patterns of calcification. A schematic drawing shows the characteristic patterns of pulmonary nodule calcification. Diffuse calcification, central calcification in nodules 2 cm or less in diameter, popcorn calcification, and laminated calcification are virtually diagnostic of a benign nodule. Diffuse, central, and laminated types of calcification are seen most commonly in calcified granulomas as a result of previous infection by tuberculosis or Histoplasma species, and popcorn calcification, albeit rare, is virtually diagnostic of hamartoma. Stippled calcification, particularly when seen in large masses, and eccentric calcification are worrisome for malignancy. They occur most commonly in pulmonary carcinoma.

Fig. 4.4, Diffuse calcification from previous tuberculosis. Frontal chest radiograph shows a diffusely calcified right upper lobe nodule (arrow) .

Fig. 4.5, Popcorn calcification in pulmonary hamartoma. Axial CT scan shows a right lower lobe smoothly marginated nodule with several coarse foci of calcification (popcorn calcification). Also note the presence of foci of fat attenuation (arrows). The findings are virtually pathognomonic of hamartoma.

Calcification within a pulmonary nodule is more readily seen on low-kilovoltage than on high-kilovoltage radiographs and much better characterized on CT than on a radiograph. Consequently, CT is the study of choice in assessing pulmonary nodules. In a study of 634 nodules assessed with CT, 153 were diagnosed correctly as benign based on the presence of central or diffuse calcification; although focal areas of calcification were identified in 13% of the primary lung tumors, only 1 carcinoid tumor had a benign pattern of calcification. The other malignant tumors had neither central nor diffuse calcification.

Calcification in malignant tumors may be seen in several circumstances: (1) most important from a differential diagnosis point of view, the isolated instance of a peripheral primary carcinoma engulfing a calcified granuloma, in which case the calcification is usually eccentric; (2) a solitary metastasis of osteogenic sarcoma or chondrosarcoma with bone formation in the osteoid or calcification of the malignant cartilage; (3) occasional primary pulmonary carcinoid tumors; and (4) calcification in large pulmonary carcinomas ( Fig. 4.6 ), particularly in tumors larger than 3 cm in diameter. The calcification in these large tumors may be punctate, chunky, or amorphous in appearance and central, peripheral, or diffuse in distribution. It is related to psammoma bodies, dystrophic calcification of necrotic carcinoma, or incorporation of a focus of previous granulomatous inflammation or calcified bronchial cartilage within the tumor.

Fig. 4.6, Calcified metastasis from breast cancer. Coronal CT scan shows a calcified nodule in the left lung. Note the eccentric distribution of the calcification. The patient also had calcified liver metastases.

Optimal assessment of lung nodules for the presence of calcification by CT requires the use of thin sections (1- to 2-mm collimation) through the nodule so as to minimize volume averaging and errors in nodule classification based on imaging appearance (e.g., solid vs. subsolid). Foci of calcification that are visible on thin-section CT usually have attenuation values of 400 Hounsfield units (HU) or higher; in the absence of such foci, attenuation values of 200 HU or higher can be considered to represent calcification.

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