Conventional Imaging of Lung Cancer

Size

The larger a nodule is at presentation, the higher the likelihood that it is malignant. For a solid, discrete pulmonary nodule, the risk of cancer is categorized according to size. A solid nodule up to 5 mm has a 1% risk of being cancer. Nodules between 6 mm and 10 mm have a 24% chance of malignancy, which increases to 33% for nodules 11 mm to 20 mm. Solid lesions greater than 20 mm in diameter have an 80% chance of malignant histology. A lesion greater than 30 mm has a 93% to 99% rate of malignancy.

Changes in nodule size are also an important prognostic consideration. Nodules that decrease in size over time are most likely infectious or inflammatory in etiology. Conversely, nodules that enlarge while under observation are considered malignant until proven otherwise. Consequently, established algorithms for managing pulmonary nodules are promulgated by the Fleischner Society. For follow-up of solid nodules, slight variations may exist, depending on the risk stratification of the individual. In a high-risk person such as a smoker, nodules up to 4 mm should have a single follow-up 12 months after presentation. Solid nodules greater than 4 mm and up to 6 mm should be reassessed by CT at 6 months to 12 months after presentation and then at 18 months to 24 months if unchanged. For nodules greater than 6 mm to 8 mm, the initial follow-up is at 3 months to 6 months, followed by reassessment at 9 months to 12 months and again at 24 months, if unchanged. Nodules greater than 8 mm may be followed-up with CT at 3 months, 9 months, and 24 months; alternatively, dynamic contrast-enhanced CT, positron emission tomography (PET), and/or biopsy could be performed. Solid nodules identified on presentation should be followed up for a minimum of 2 years to establish stability and benignity. Interval nodule growth should prompt further workup, including biopsy.

Density

Solid nodules have a low overall malignancy rate of 7%. Subsolid nodules have a greater chance of being malignant than solid nodules and may represent primary adenocarcinomas of the lung.

Ground-Glass Opacity

Pure ground-glass lesions, those lesions with homogeneous transparent density through which underlying architectural features are seen, have an 18% chance of being malignant. Very small ground-glass nodules, up to 5 mm, may reflect atypical adenomatous hyperplasia, which is premalignant and does not require CT follow-up, according to the Fleischner Society recommendations for subsolid nodules. For lesions greater than 5 mm, the differential diagnosis includes focal fibrosis, atypical adenomatous hyperplasia, and indolent primary adenocarcinoma. Neoplasms with pure ground-glass attenuation usually correspond with adenocarcinoma in situ, the type A lesion in the Noguchi classification scheme of pulmonary adenocarcinomas, although rarely, they may be of mixed subtype. Heterogeneous ground-glass lesions or lesions with internal alveolar collapse are compatible with Noguchi type B lesions. Ground-glass adenocarcinomas have doubling times on the order of 384 days to 567 days.

The presence of solid components mixed with ground-glass attenuation denotes a mixed-density, part solid nodule (PSN). These part solid and part ground-glass nodules have the highest malignancy rate (63%). The larger size of the solid features is associated with worse prognosis; these lesions correspond to Noguchi types B and C ( Fig. 21.2 ). The development of solid density within a pure ground-glass opacity (GGO) under surveillance is an indication of transformation to a more aggressive lesion. An increase in diameter in an observed GGO is also a sign of progression ( Fig. 21.3 ). Papillary, tubular, acinar, and other subtypes of lung adenocarcinoma on imaging cannot be reliably distinguished; rather, the diagnosis is histologic.

Initial follow-up for both pure GGOs and PSNs is performed 3 months after presentation to distinguish a potentially infectious or inflammatory lesion, which would be expected to decrease or resolve in this period. Single GGOs greater than 5 mm in diameter that persist after 3 months without change should be reassessed annually for a minimum of 3 years, unless or until they show progression. Solitary PSNs are managed according to the size of the solid component. If the solid portion is less than 5 mm, follow-up for the nodule may be similar to that for a GGO, for a minimum of 3 years. Lesions with larger solid components persistent after 3 months should be reassessed by biopsy and/or resected.

The presence of several GGOs and/or mixed-density lesions makes resection of all lesions impossible for some individuals. Multiple GGOs 5 mm or less should have a follow-up CT at 2 years and again at 4 years after presentation, in the absence of interval changes. Pure GGOs greater than 5 mm without a dominant lesion should undergo annual surveillance similar to that for a single GGO. Careful follow-up of these GGOs should be done in order to identify candidate tumors for limited resection based on progression or aggressive transformation. When a dominant lesion or lesions with part solid components are present in the setting of other nodules, biopsy and/or lung-sparing surgical resection is advised.

Enhancement

Neoplastic pulmonary nodules have been shown to have increased vascularity compared with benign nodules, suggesting that nodule enhancement can be used as a distinguishing characteristic in evaluating indeterminate solid lesions. The assessment process requires noncontrast CT images through the pulmonary nodule, which is then imaged at specific time points up to 4 minutes after administering intravenous contrast medium. Hounsfield unit (HU) attenuation measurements are taken with a region of interest for every time point and the differential enhancement is calculated. A difference of 15 HU or less is strongly suggestive of benignity. With a 15-HU threshold, investigators have found 98% sensitivity but 58% specificity for malignancy. Another study using a threshold of 30 HU with multidetector CT demonstrated 99% sensitivity for malignancy, with 54% specificity, a positive predictive value of 71%, and a negative predictive value of 87%. Nevertheless, because of time constraints, need for technical expertise, availability of other noninvasive assessment methods such as PET–CT, and radiation dose to the patient, nodule enhancement studies are not frequently performed in the nonacademic clinical setting. More recently, dual-energy CT, which has the capability of creating a virtual noncontrast image, has been investigated as a potential method of measuring nodule enhancement without multiple acquisitions, thus minimizing the radiation dose.

Borders

A nodule with an irregular or shaggy border can raise suspicion for malignancy; however, infectious and inflammatory nodules may have a similar appearance. The degree of suspicion may rest on the overall constellation of radiographic findings, the individual’s symptoms and demographic characteristics, and persistence over time. Cancers may be multilobulated, although smooth and well-circumscribed nodules may be malignant 21% of the time. Spiculation in the periphery of a nodule correlates pathologically with a desmoplastic reaction of the nodule or tumor infiltration into the surrounding lung parenchyma and is present much more frequently in malignant nodules. Many lung cancers are ill defined, hindering detection on radiographs.

Shape

Although most lung cancers manifest as a nodule or mass, the overall shape of carcinomas varies. Some adenocarcinomas, particularly the mucin-producing subtype, can present as ill-defined parenchymal consolidation caused by mucin filling the alveoli; this is radiographically indistinguishable from pneumonia but will persist despite antibiotic treatment ( Fig. 21.4 ). An uncommon manifestation of early lung cancer is a focally thickened or impacted bronchus, sometimes with peripheral inflammatory changes.

Calcification

Calcifications within a nodule can be evaluated according to their pattern. Benign calcifications are central, diffuse, laminar, or so-called popcorn in shape. Eccentric calcification is associated with malignancy. Nonetheless, preexisting calcifications in the lungs such as granulomas may become engulfed by a tumor, and carcinoid tumors can have punctate calcifications, making the presence of calcification less reliable in determination of benign disease.

Adipose Content

Macroscopic fat within a pulmonary nodule can be identified visually and is measurable with a region of interest; HU measurement less than 1 is compatible with adipose tissue. The presence of macroscopic fat is an indication of benignity and favors the diagnosis of hamartoma, a smooth muscle neoplasm having no malignant potential. However, low attenuation in a nodule without the presence of actual fat can suggest necrosis or the presence of mucin.

Cavitation

Up to 22% of primary lung cancers demonstrate cavitation on CT imaging. Squamous cell carcinomas of the lung are the most likely to exhibit this feature; however, primary lung adenocarcinomas will also cavitate. One type of cavitation occurs when tumors outgrow their blood supply and undergo central necrosis. Some adenocarcinomas exhibit a phenomenon of pseudocavitation caused by bronchial or alveolar expansion within the tumor ( Fig. 21.5 ). It is also possible for a lung cancer to arise in the wall of a preexisting cystic space.

Nevertheless, infectious processes of the lung, including mycobacterial, fungal, and bacterial pneumonias, can also cavitate, as can nodules related to vasculitis. Some early studies demonstrated that cavity wall thickness measured on radiographs could be a discriminating feature in distinguishing nonmalignant from malignant disease; however, results of other studies using CT have suggested that measuring wall thickness is not as useful. Both inner cavity wall irregularity and notching, or focal lobulation of the outer cavity wall, have both been shown to occur more frequently in malignant than in benign cavitary lesions.

Multiplicity

The implication of more than one lesion also depends on size and density. Multiple small, solid nodules that are smaller than 6 mm are most likely to be postinfectious/postinflammatory and are considered low risk for malignancy. Conversely, numerous ground-glass nodules and/or PSNs are highly suggestive of multifocal synchronous primary adenocarcinomas. The presence of two synchronous primary lung carcinomas of different histologic types is also possible but uncommon.

Location

Lung cancers may be located in the peripheral or central aspect of the lungs. Statistically, more malignancies are found in the upper lobes, especially the right upper lobe.

Technical Factors

The radiograph itself may be of limited quality for a variety of technical reasons, including overpenetration or underpenetration of the chest by the photon beam or positioning variances such as rotation or lordosis. Objects external to the patient may cause artifacts. Although metal objects such as jewelry and clothing fasteners are easy to identify, nonmetal items such as buttons, hair, or clothing decorations may be confounding. Parts of the lung may be excluded from the field of view by faulty technique. Lastly, the ability of the patient to achieve full lung inspiration on the radiograph affects the conspicuity of lesions. Visualization of nodules is enhanced by using higher peak kilovoltage (140 kVp), which accentuates contrast.

Blind Spots on Radiography

Chest radiographs can have blind spots, many of them due to overlapping anatomic structures such as skeletal bones. Specific regions such as the hila, where the pulmonary arteries and veins and the airways converge, may also be difficult to evaluate ( Fig. 21.6 ). Superimposed acute processes may mask findings of malignancy. Not infrequently, pneumonia can be the first indication of a central obstructing or partially obstructing lesion. Recurrent consolidations in the same location are highly suspicious ( Fig. 21.7 ). Consequently, radiographic follow-up to document resolution of pneumonia is advised. Chronic lung disease such as pulmonary fibrosis may also hinder identification of a focal abnormality. It is worth noting that preexisting chronic lung disease is a risk factor for lung cancer.

Characteristics of Lung Cancers Missed on Radiography

Retrospective studies of lung cancers not prospectively identified on chest radiography have demonstrated several common characteristics. In general, missed lung cancers were located in the upper lobes, although one study showed no difference in the location of missed and detected lung cancers. Another characteristic was small nodule size, on average 16 mm to 19 mm. An analysis of size differences in detection rate indicated that nodules 10 mm or smaller were missed 71% of the time. Nodules 10 mm to 30 mm in size were not detected 28% of the time. However, nodules 30 mm to 40 mm were missed at a rate of 12%, and nodules greater than 40 mm were identified 100% of the time. Centrally located nodules that were missed had a larger circumference than overlooked peripheral nodules. Overlying anatomic structures contributed to difficulty in detecting lung cancers. Many of the missed cancers had ill-defined borders and relatively low levels of density. A high pretest probability of lung cancer has been shown to promote detection rates, and in two studies, underdiagnosis of lung cancers in women appeared to be related to lower clinical suspicion.

Use of Special Radiographic Views

Disagreement exists over the importance of lateral projection in making a diagnosis of lung cancer. The authors of several studies have discovered a few cancers that could be visualized only on the lateral radiograph; although this represents a small number of cases, there is support for continued acquisition of the lateral chest radiograph in conjunction with the posteroanterior view ( Fig. 21.8 ). Oblique radiographs may also be helpful in determining whether an abnormality seen on standard views is external to the patient.