A solitary pulmonary nodule (SPN) is the most common radiographic presentation of lung cancer. The imaging characteristics of solitary pulmonary nodules are described and illustrated. The appearance and implications of extension of lung cancer to the pleura are explored. Finally, the contribution of various thoracic imaging modalities to the diagnosis and staging of lung cancer are discussed briefly.[ONCOLOGY 11(9):1387-1402]
Over 95% of all primary lung tumors are bronchogenic carcinomas. These are subdivided into four main cell types: squamous cell carcinoma, small-cell carcinoma, adenocarcinoma, and large-cell carcinoma. The relative incidence of these four cell types has changed over the last 30 years, with the number of squamous cell tumors decreasing and the number of adenocarcinomas increasing. This reflects a change in the biology of lung cancer.
Although none of the four main cell types is exclusively central or peripheral in location, the majority of small-cell lung cancers and squamous cell carcinomas are centrally located. This is in contrast to most adenocarcinomas and large-cell tumors, which tend to be peripheral.
Among the more common central tumors, squamous cell carcinoma is more frequently associated with bronchial obstruction, a hilar mass, and cavitation. Small-cell carcinoma is often characterized by extensive, bulky mediastinal lymphadenopathy. Small-cell carcinoma is less likely than squamous cell carcinoma to produce bronchial obstruction.
A solitary pulmonary nodule (SPN) is a single round or oval opacity in the pulmonary parenchyma measuring < 3 cm in diameter and completely surrounded by pleura (Figure 1). The reported incidence of malignancy in a solitary pulmonary nodule varies from 3% to 6% in mass surveys of the general population to 30% to 60% of resected solitary pulmonary nodules.
The radiologic work-up of the solitary pulmonary nodule is pursued to facilitate the resection of potentially curable lung cancers and to minimize the resection of benign nodules. Neoplasm can often be strongly suspected or excluded based on the radiologic characteristics of the solitary pulmonary nodule.
As a general rule, SPNs > 3 cm in diameter are more likely to be malignant. The growth rate of a solitary pulmonary nodule is quantitated by measuring its doubling time, ie, the time it takes to double in volume. The detection of a solitary pulmonary nodule on chest films depends on its size, density, and edge characteristics.
Nodules must be at least 9 mm in diameter before they can be reliably detected on chest plain films. Work done by Geddes indicates that the natural history of a lung malignancy is to double its volume 40 times before death ensues. On reaching the reliably detectable size of 9 mm, a nodule has already undergone 30 doublings. A single doubling of the volume of an SPN produces a relatively small increase in its transverse diameter. Doubling times of between 7 and 465 days are strongly suggestive of malignancy, whereas doubling times that are either shorter or longer than this suggest a benign etiology.
According to Gurney, a 9-mm SPN with a doubling time of 100 days will measure 1.1 cm at 3 months and 1.4 cm at 6 months. Therefore, should the physician opt for radiographic surveillance following discovery of an SPN, accurate measurement is of the utmost importance. Follow-up radiographs should always be compared to the initial radiograph showing the solitary pulmonary nodule. Discovery of a solitary pulmonary nodule on chest radiographs should prompt every effort to obtain more remote chest films for comparison. A retrospective analysis may yield valuable diagnostic information. The absence of growth over a 2-year period is the most reliable indicator of benignity.
On rare occasions (1 case per 750,000), a bronchogenic malignancy may show spontaneous regression. More frequently, lung cancers may exhibit a temporary reduction in size followed by a resumption of growth. This reduction in size suggests a resolving inflammatory process. It is thought to be due to partial interruption of the tumor's blood supply, resulting in infarction and necrosis of a portion of the mass. The ensuing fibrosis and retraction may result in an overall decrease in the volume of the mass.
Webb notes that, occasionally, as a pulmonary nodule grows, it may become less well defined, and thus, appear smaller on chest films. Cross-sectional CT imaging will provide clarification if the margins of the opacity are unclear on conventional chest films.
Siegelman et al,[10-12] Proto and Thomas, and Zerhouni et al have extensively investigated nodule densitometry using CT. Compared with conventional chest films, CT is 10 to 20 times more sensitive to differences in density. By using this imaging modality, a number of nodules judged to be noncalcified by conventional radiography can be classified as benign on the basis of their attenuation coefficients.
Huston and Muhm reported that a CT nodule densitometric study (phantom reference) combined with conventional trispiral tomography had a 77% accuracy in the diagnosis of solitary pulmonary nodules. Despite the effectiveness of this technique, almost one-fourth of noncalcified solitary pulmonary nodules remain indeterminate. A number of false-negative densitometry studies have also been reported.
The distribution of calcification within the SPN is of the utmost diagnostic importance. The presence of a thin layer or layers of calcium in a lamellar pattern is indicative of a granuloma, usually a histoplasmoma (Figure 2). Central calcification may also be seen in granulomas. Caution must be exercised when assessing solitary pulmonary nodules for the presence of central calcification, as, occasionally, a growing lung cancer may engulf a calcified granuloma or a scar carcinoma may arise within a preexisting calcified granuloma (Figure 3).
"Popcorn" calcification is associated with hamartomas. These benign lesions arise from small rests of tissue not normally found in the lung. The presence of cartilaginous elements gives rise to the popcorn calcification.
Calcification may also be seen in both primary and metastatic tumors to the lungs. Specimen radiography performed by O'Keefe et al demonstrated the presence of calcification in 14% of resected primary lung tumors. Several individual case reports have described malignant pulmonary nodules with high CT numbers and central calcification.[18-20]
Although the interface between the SPN and the normal surrounding lung cannot be used as an absolute indicator of the nature of the lesion, it can provide useful information. A smooth peripheral margin on CT is more frequently associated with benign lesions than with malignant tumors. The converse is also true.
Zwirewich et al assessed a total of 96 solitary pulmonary nodules (85 malignant, 11 benign) by CT. Spiculation, defined as linear strands extending from the nodule margin into the lung parenchyma but not extending to the pleural margin, was present in approximately 90% of primary carcinomas. It was also seen in 5 of the 11 benign lesions.
A pleural tag was defined as a linear area of high attenuation surrounded by aerated lung, originating from the edge of the mass and extending peripherally to contact the pleural surface (Figure 4). Pleural tags were seen in 58% of malignant lesions and 27% of benign lesions. Both spiculation and pleural tags correlated pathologically with a desmoplastic response.
Lobulation (Figure 5) was predominantly associated with malignancy. This finding correlated with nodular excrescences of the tumor at its leading edge.
Cavitation is seen in 2% to 16% of lung cancers.[22,23] Usually, the cavity wall is thick (> 5 mm at its thickest portion) and may demonstrate a nodular internal margin due to focal tumor excrescences. Occasionally, a thin-walled cavity may be associated with malignancy.
Woodring et al evaluated the wall thickness of cavitary SPNs and found that 94% (29/31) of cavities with a wall thickness £ 4 mm were benign. The two remaining thin-walled cavities had a maximum wall thickness of 2 mm and were malignancies. In the same series, the authors found that 95% of cavitary solitary pulmonary nodules with a wall thickness > 15 mm were malignant (Figure 6). Lesions with a wall thickness between 5 and 15 mm were almost equally divided between benign and malignant. The authors also noted that a smooth inner wall to the cavity was more commonly observed in lesions of benign etiology. A cavitary solitary pulmonary nodule should always raise the question of malignancy, and, in the absence of a definitive diagnosis, a diagnostic procedure or close radiographic follow-up is required.
In the 1980s, the radiologic assessment of the solitary pulmonary nodule focused primarily on CT densitometry. In the 1990s, two techniques that focus on vascularity, pathophysiologic features, and pharmacodynamics have been applied to the diagnosis of the solitary pulmonary nodule.
Contrast-Enhanced Thin-Slice CT—The first of these techniques is based on differential nodule enhancement with IV contrast material, as measured with thin-slice CT. It relies on both qualitative and quantitative differences in the blood supply of benign vs malignant lung lesions. Nodule enhancement following the administration of IV contrast material depends on the amount of contrast that enters the extravascular space of the nodule and the vascularity of the nodule.[25,26]
Swensen and colleagues found a 20-Hounsfield-unit increase in 24 of 30 solitary pulmonary nodules subsequent to the IV administration of 100 mL of contrast material. Of the 24 nodules showing contrast enhancement, 23 were malignant. This work suggests that assessment of CT enhancement of the solitary pulmonary nodule may be useful in gauging the likelihood of malignancy.
FDG-PET—The second technique currently being evaluated to differentiate between benign and malignant SPNs is PET scanning with 2[F-18]-fluoro-2-deoxy-d-glucose (FDG). This technique is based on the increased glucose metabolism characteristic of tumor cells. Nonmalignant entities fail to show glucose hypermetabolism.
Gupta et al used FDG-PET imaging to evaluate 30 patients with solitary noncalcified pulmonary nodules. Thirteen biopsy-proven malignant nodules demonstrated increased FDG uptake, whereas seven benign solitary pulmonary nodules showed no increased FDG uptake. These data and work by Patz et al suggest that FDG-PET scanning can accurately distinguish benign from malignant focal lung lesions.