Solitary Pulmonary Nodule
A solitary pulmonary nodule found on a plain-chest radiograph should be further analyzed with CT to characterize the nodule, determine whether additional nodules are present, and assess other associated findings, including lymphadenopathy and pleural effusions.2,4,7–10 The term mass is reserved for large nodules; over time, the definition has decreased progressively from 6 to 4 cm to, most recently, 3 cm. The size of a nodule itself correlates positively with the probability of malignancy, even in the absence of additional features to suggest malignancy. The margins of the nodule, pattern of calcification (if present), and presence or absence of fat help to distinguish benign from malignant lung nodules. Special features such as enlarged feeding and draining vessels also can help to indicate a very specific diagnosis. A nodule containing dense central calcification, whether solid or lamellated, is benign, requiring no further follow-up to determine the nature of a calcified granuloma. Thin-slice soft tissue reconstruction of CT data provides the most accurate assessment in this regard.11 The common causes of solitary pulmonary nodules are listed in Table 3-2.
Table 3-2Differential Diagnosis for Solitary Pulmonary Nodules ||Download (.pdf) Table 3-2Differential Diagnosis for Solitary Pulmonary Nodules
|NODULE ETIOLOGY ||DISTINGUISHING CHARACTERISTICS |
|Granuloma ||Smooth margins |
Solid or lamellated calcifications
|Carcinoid ||Lobulated margins |
Dystrophic, eccentric calcifications
|Hamartoma ||Lobulated margins |
Calcifications appear in rings or arcs
|AVM ||Lobulated margins |
Infrequent calcification (vascular)
|Lung cancer ||Spiculated, lobulated, or smooth margins |
Large lesions with necrosis
Cavitation in squamous cell carcinoma and adenocarcinoma
|AIS/MIA ||≤5 mm of atypical adenomatous hyperplasia |
Focal extensions to pleura
Very slow growth
|Solid pulmonary metastasis ||Nonspecific, although may have appearance characteristic of primary tumor |
Solitary pulmonary nodules and small solid nodules are studied with serial CT examinations over 2 or more years to determine whether a nodule is benign or malignant. One outcome of screening studies such as the Early Lung Cancer Action Project is recognition of the extremely low incidence of cancer in tiny nodules.12 This observation contributed to the Fleischner Society Guidelines, which currently recommend only a single follow-up CT scan for solitary pulmonary nodules that measure less than 4 mm in diameter and then only in high-risk patients (Tables 3-1 to 3-3). Clinical practitioners have yet to become comfortable with this “no follow-up” recommendation for patients at low risk of developing lung cancer, but this change has definitely increased patient and practitioner comfort with the 6- to 12-month interval surveillance CT.
Table 3-3Differential Diagnosis of Mediastinal Masses ||Download (.pdf) Table 3-3Differential Diagnosis of Mediastinal Masses
|MASS ||DIFFERENTIAL DIAGNOSIS ||LOCATION ||FEATURES |
|Anterior mediastinal mass ||Thyroid mass |
Thymoma or thymic cyst
Lymphoma and small cell lung cancer
|Contiguous with thyroid gland |
All lymph node stations in superior mediastinum, thymic bed, prevascular space, aorticopulmonic window
Extramediastinal location hilar lymph nodes
|Deviation of trachea |
May be lobulated
Mass may involve multiple lymph node groups
Hilar lymph node enlargement may be asymmetric
Hodgkin disease spreads from thymic bed to
middle mediastinum to hilar lymph nodes
| ||Germ cell tumor ||Variable, including prevascular space and thymic bed ||Fat, hair, and teeth are diagnostic |
May be homogeneous with smooth margins
|Middle mediastinal mass ||Duplication cyst (includes bronchogenic cyst) ||Most often located at bifurcation of |
trachea and central airways
May be paraesophageal or intraparenchymal
|Smoothly marginated |
| ||Lymphadenopathy ||All lymph node stations, including |
|May appear as separate enlarged nodes or as a multiple lymph node mass |
May be homogeneous or heterogeneous
Low attenuation indicates tuberculosis
Single site with enhancement indicates Castleman disease
| ||Pericardial cyst ||Adjacent to heart, especially in cardiophrenic sulcus ||Smoothly marginated |
Can also represent pericardial diverticulum if history of mediastinoscopy
| ||Thyroid mass (intrathoracic goiter) ||Thyroid, extending into thorax |
15% of these masses extend behind the trachea
|Appearance of thyroid tissue is heterogeneous, can include calcifications and focal fluid |
| ||Tracheal tumor ||Within or surrounding trachea ||Narrowing of trachea |
Adenoid cystic carcinoma has more tumor outside the trachea than within it, so-called toothpaste lesion
| ||Vascular variants and |
|Posterior to trachea |
Anterior or posterior to esophagus
|Diverticulum of Kommerall with aberrant subclavian artery |
Vascular rings and slings
|Posterior mediastinal mass ||Esophageal abnormalities and masses ||Large esophageal mass can occupy middle and posterior mediastinal compartments ||Esophageal cancer |
Foregut duplication cyst
| ||Neurogenic tumor ||Connected to neural foramen ||Smoothly marginated or lobulated |
May have low attenuation
May contain fat
| ||Extramedullary hematopoiesis ||Paraspinal masses ||Masses are often paired |
Granulomas are the result of inflammatory processes and may vary in size as well as presence of calcification. Since the dense, solid, calcified nodule can vary in size, it is important to remember that such nodules are benign calcified granulomas. Granulomas are not necessarily calcified, though. A solitary noncalcified granuloma must be treated as an indeterminate pulmonary nodule. It is helpful to consider the prevalence of granulomatous disease in the patient population, which also will reflect the presence of endemic granulomatous diseases in the community. The size of the nodule is also a factor because tiny nodules, measuring less than 4 mm in diameter, rarely signify early malignancy.
Hamartomas can contain specific calcifications, described as rings and arcs, owing to cartilage that may be present within the hamartoma. Fat also may be seen in the same pulmonary nodule. As with carcinoid tumors, hamartomas also may have a lobulated contour. In the case of a hamartoma, the identification of fat on thin-section images is the most convincing evidence of benignity. Fat also can be seen in nodules or even consolidations if the lesion is caused by the aspiration of mineral oil, commonly referred to as lipoid pneumonia.
Arteriovenous malformations (AVMs) may be single or multiple, as in the case of syndrome such as Osler–Weber–Rendu syndrome of hereditary hemorrhagic telangiectasia (HHT). Enlarging vessels leading to nodules are most helpful for identification. Contrast-enhanced CT scanning with PE protocol for vessel enhancement may identify additional more subtle lesions. Very small lesions may only be detected by echocardiographic bubble study. Although an AVM is not malignant, complications can include bleeding and spread of infection from lung through systemic circulation to seed brain abscesses. Treatment options include interventional radiologic embolization as well as surgery.
The recognition of malignant potential in small nodules has increased through more than a decade of lung cancer screening trials and is now well supported by CT technology allowing volumetric imaging of nodules with slice thicknesses of less than 1 mm. The relationship to mortality risk from these lesions is less clear than the radiopathologic correlation consistently demonstrated. Through such radiopathologic correlations, we have learned that invasive adenocarcinoma is often present in the lesions described previously as BAC owing to lepidic growth characteristics13,14 (Fig. 3-21). The increased understanding of the significance of specific features of nonsolid and part-solid nodules and the progression of adenocarcinoma in situ to invasive adenocarcinoma has resulted in earlier resection of many such lung cancers. The lepidic growth of tumor along alveolar walls defines both atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS, formerly BAC). Only size distinguishes between these two entities, with AAH used to describe ground-glass opacities up to 5 mm in diameter and AIS used to describe lesions larger than 5 mm in diameter. The diagnosis no longer rests on morphology, which has been replaced by emerging biomarkers that allow analysis of transthoracic biopsy specimens chiefly by cytology to provide diagnosis and necessary biomarkers for selecting chemotherapy, obviating the need for many excisional biopsies.
Transaxial 1-mm HRCT image of the chest rendered for lungs at the level of the aortic arch reveals adenocarcinoma with AIS features in the periphery of the left upper lobe. It contains a solid component anteriorly, ground-glass opacity medially and posteriorly, along with a small cystic feature centrally and focal radiations extending to the pleural surface anteriorly and laterally.
On CT, the presence of lepidic growth can have the appearance of well demarcated but subtle ground-glass opacity, which, by definition, allows visualization of vessels and airways within the nodule. The importance of these subtle opacities, particularly when present with findings suggestive of more advanced lung cancer, has caused them to be reclassified as nonsolid nodules. As the tumor increases, such nodules develop areas of more solid opacity that can result in a part-solid nodule. In this context, the development of bars corresponds to invasive adenocarcinoma. Small cysts, some of which may be indistinguishable from bronchi, and focal extensions to pleural surfaces, with and without deflection of the pleural reflection, are also seen. Since these lesions can be unifocal or multifocal and require different treatment strategies, extensive follow-up CT scanning is performed. Comparison of size measurements also has become more complex as tumor evolution has become better demonstrated on CT scans. Tumor progression may be expressed by increase in density of part or all of the well-demarcated ground-glass opacity accompanied by decrease in size of the lesion or a part of the lesion. Thin-section reconstruction in lung kernel provides the most consistent data for comparison. Short-term follow-up reveals resolution of many such opacities, particularly after a course of antibiotic therapy. In the case of persistent ground-glass opacity, more than 2 years of follow-up may be required to prove the lack of growth over time.
The new WHO classification for lung cancer places carcinoid tumors within the category of lung cancer, regardless of whether typical or atypical, in the spectrum of neuroendocrine malignancies, which also include small cell lung cancer.15 Carcinoid tumors present as endobronchial lesions with a cherry-like appearance on bronchoscopy, often associated with mucoid impaction of the distal airways. Dystrophic calcification in a lobulated nodule seen obstructing a bronchus, perhaps with mucoid impaction also evident, is a classic description of a carcinoid tumor. Not all carcinoid tumors have every one of these features; however, and the presence or absence of individual imaging features does not correlate with typical versus atypical carcinoid. The most extreme form of neuroendocrine tumor, small cell lung cancer, may present with no obvious lung nodule but with striking lymph node enlargement.
The presence of tumor elsewhere in the body also may increase concern for metastasis, although the lung nodule may be the initial presentation of an extrathoracic malignancy. Colon cancer, common in the age group of patients who develop lung cancer, is particularly associated with large “cannon ball” and potentially solitary pulmonary metastases.
Mediastinal masses can be tricky to image with CT. The most difficult decision is regarding the administration of intravenous contrast material. If a patient has a thyroid mass that can be treated with radioactive 131I, the administration of iodine contrast material is contraindicated. The administered iodine contrast material would saturate the iodine receptors to which radioactive 131I also binds, requiring a 3-month delay in treatment to allow the receptors to become available again to 131I. Not giving iodine contrast material, on the other hand, masks the diagnosis of Castleman disease. In the case of Castleman disease, or angiofollicular lymph node hyperplasia, the enhancement of the mass is most apparent by comparing scans before and after the administration of intravenous contrast material. Adopting the strategy of paired CT scans with and without contrast material for all nonthyroid mass examinations unnecessarily increases the radiation exposure for most patients. Thymoma, lymphoma, and teratoma may be imaged with or without contrast material. Contrast material sometimes adds clarity to the examination of mediastinal masses. The age of the patient is generally more helpful than contrast enhancement with these tumors (Fig. 3-22).
Transaxial 5-mm non–contrast-enhanced images of the chest rendered for mediastinum reveal a homogeneous, smoothly marginated mass in the right side of the thymic bed. This appearance is classic for a thymoma, especially when seen in middle age.
Extensive Pleural Disease—Diffuse Malignant Pleural Mesothelioma
The pleural space is not well vascularized and therefore can provide an environment for infection that is not easily treated with antibiotics. Hence extensive pleural disease requires attention from the thoracic surgeon whether it is benign or malignant. Since 800 mL of pleural fluid or a change in pleural fluid volume of this magnitude can be undetectable on a bedside chest radiograph, pleural effusions detected by imaging are often significant. The characterization of small, medium, and large for the size of a pleural effusion is a gross approximation on chest radiographs, although such imaging may be more helpful for quantification than CT and MRI. Differences in patient position during the examination make it difficult to directly compare the sizes of pleural effusions over time using different modalities. The volume of a pleural effusion is often overstated on cross-sectional imaging reports compared with chest radiography. In the absence of quantification, the size of a pleural effusion on axial CT images is often determined by cranial-caudal extent, resulting in overestimation of the size of many significant pleural effusions. The same problem also applies to reporting the size of a pneumothorax. As image processing enters the clinical practice of radiology, more quantification may be provided on a routine basis. The more pressing issue in this regard is in the setting of primary pleural tumor with extensive pleural disease, such as in malignant pleural mesothelioma. Fluid and tumor masses may encase the lung with a thickness that warrants measurement despite the complexities involved. In some instances, the additional findings such as extrathoracic lymph nodes and invasion of vital structures, whether in the mediastinum or the abdomen or by extensive involvement of the chest wall, may be more important than quantification of tumor mass, fluid, or both within the pleural space (Fig. 3-23).
Coronal MRI and transaxial CT images demonstrate lobulated pleural thickening with small collections of fluid encasing the right lung. MRI demonstrates the fascial plane between the pleural disease and the chest wall, diaphragm, and mediastinum. Note the extrapleural lymph nodes in the right anterior diaphragmatic region on the bottom CT image.
Since the pleural surface is very thin, pleurectomy may not be recognized on postoperative CT. Adjacent hemorrhage is often seen without conveying its postoperative significance. The performance of the extrapleural pneumonectomy (see Chapter 119), most often for malignant pleural mesothelioma but also on occasion appropriate for the more common adenocarcinomatosis of the pleural space and unusual tumor metastases, requires careful consideration of preoperative cross-sectional imaging, generally with CT, MRI, and PET/CT.16 The use of ultrasound is limited primarily to the localization of small collections of pleural fluid. Imaging modalities generally are complementary, but caution is warranted regarding the limitation of each modality in the assessment of extensive pleural disease.
Contrast-enhanced chest CT is the most basic of these imaging techniques, but it can be the best imaging modality for detection of small extrathoracic lymph nodes, chest wall tumors, and bone destruction. CT is not sensitive to focal invasion of the abdomen and may overestimate invasion of mediastinal structures by contiguous tumor. Secondary signs, such as a pericardial effusion in the setting of pericardial invasion, may be helpful for correct assessment of disease extent by CT. Multiplanar reconstruction has increased the utility of the volumetric CT data conventionally acquired by multidetector CT.
MRI, performed with multiplanar T1- and T2-weighted sequences and intravenous injection of 20 mL of gadolinium contrast agent, provides the best demonstration of fascial planes. In particular, sagittal MRI provides the best preoperative evaluation for the integrity of the hemidiaphragm, and all three planes contribute in a similar manner to detection of mediastinal fascial planes. MRI demonstration of tissue characteristics also highlights the distinction between tumor masses and fluid in the pleural space. Diffusion characteristics may allow preoperative determination of epithelial and sarcomatoid tumor subtypes and be useful in selection of biopsy site. MRI provides less spatial resolution and may not image small structures, including tiny lung nodules, even when the structure is within the image. Furthermore, MRI sequences are not volumetric in the manner of CT scans and thus can fail to image small structures.
PET/CT is not always performed; however, it is being used increasingly to select the best possible biopsy target, thereby improving the initial diagnosis of malignant pleural mesothelioma. Multimodality therapy also may be offered on the basis of PET/CT findings, particularly when intense 18F-FDG activity is seen in extrathoracic lymph nodes despite being smaller than can reliably be detected by the radioisotope and smaller than can be reliably identified by contrast-enhanced CT. Volumetric measurement of tumor burden also will be enhanced by functional information from PET scanning. Consequent improvements in the evaluation of treatment for malignant pleural mesothelioma also can lead to the use of PET/CT for evaluation of treatment adequacy in benign processes such as empyema.
Horizons: CT screening and tumor ablation
The use of CT to improve survival of lung cancer patients is no longer controversial as it is widely accepted that CT will find smaller, presumably earlier lesions, whether it is the patient's first lung cancer, a recurrent lung cancer, or independent development of a new lung cancer in a patient who already has had lung cancer. For more than 50 years, screening trials failed to demonstrate decreased lung cancer–specific mortality. In 2011, the National Lung Screening Trial (NLST) succeeded for the first time in demonstrating a lung cancer–specific mortality reduction of 20% through low-dose lung cancer screening CT.17 In 2012, the American Association for Thoracic Surgery (AATS) published guidelines for the provision of lung cancer screening also to include provision of equivalent low-dose screening CT (LDCT) scan surveillance to long-term lung cancer survivors after the surveillance period for recurrence.4 Lung cancer screening CT scans should strive to maintain dose equivalent to NLST recommendations (1.5 mSv) and should be undertaken with a multidisciplinary team including board-certified thoracic surgeons to ensure the very lowest morbidity and mortality that is necessary for results comparable to the NLST.
The use of imaging for screening of patients at high risk for developing lung cancer may change significantly over the next few years. In addition to guidelines regarding who should receive CT, at what age, and at what intervals in time, we may well see the introduction of a biomarker screening test for lung cancer. Image-guided therapy and the introduction of new drugs to treat tumors will further hone diagnostic evaluation with imaging and shape the future practice of thoracic surgery.
Pulmonary thermal ablation, initially performed with radiofrequency (RF) electrodes for palliation in nonoperative candidates, is likely to be superseded by microwave ablation that would be a more suitable treatment strategy for early lung cancer.18,19 The advantage of microwave energy over RF and laser is the larger and faster volume of tissue heating that allows more complete ablation of larger tumors. Microwave energy provides greater control over the size and shape of the ablation zone and is able to reduce the effect on adjacent blood and airflow, thereby reducing complications seen with RF ablation. This therapy ultimately may become part of a multimodality approach to lung cancer, requiring less radical surgery and permitting cure of patients who are presently unsuitable candidates for surgery. Microwave ablation may provide effective therapy, capable of replacing resection for early lung cancers, particularly in the elderly.