- Email: [email protected]
Radiologic evaluation of the solitary pulmonary nodule
Radiologic Evaluation of the Solitary Pulmonary Nodule Thomas E. Hartman, MD The radiologic evaluation of solitary pulmonary nodules can be a complex process. Modalities, which can be used, include the chest radiograph, computed tomography, and positron emission tomography scanning. Interventional radiology can also play a role with image-guided transthoracic needle aspiration of indeterminate pulmonary nodules. The primary role of radiologic evaluation is to try to differentiate benign from malignant pulmonary nodules. The imaging findings that can be helpful in making this distinction as well as the limitations of each of the modalities are discussed. For the purpose of this review, solitary pulmonary nodule mimics such as skin or rib lesions, vascular malformations, and areas of rounded atelectasis are not discussed. Copyright 2002, Elsevier Science (USA). All rights reserved. Key words: Coin lesion, pulmonary, lung neoplasm, computed tomography.
S
olitary pulmonary nodules (SPN) are round or oval areas of increased opacity in the lung on a chest radiograph that measure less than 3 cm in diameter. These nodules can be caused by a variety of disorders including neoplasms, infection, inflammation, and vascular and congenital abnormalities. In 1991, it was estimated that approximately 150,000 solitary pulmonary nodules were detected in the United States annually.1 Many of these are discovered incidentally at chest radiography (Fig 1) or computed tomography (CT). Although most SPNs are benign, up to 40% of these nodules may be malignant.2-4 With the advent of low-dose screening for lung cancer, the incidence of solitary pulmonary nodules, which requires further evaluation, is likely to increase.
Chest Radiograph Standard radiologic evaluation of pulmonary nodules on the chest radiograph has the primary function of trying to differentiate benign from malignant lesions. There are certain imaging criteria on the chest radiograph or CT that can be used to predict the likelihood of a nodule being benign or malignant. The two primary criteria for From the Department of Radiology, Mayo Clinic, Rochester, MN. Address reprint requests to Thomas E. Hartman, MD, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Copyright 2002, Elsevier Science (USA). All rights reserved. 1043-0679/02/1403-0000$35.00/0 doi:10.1053/stcs.2002.33155
the evaluation of SPNs are time and calcification within the nodule. Other criteria that may be helpful include margins of the lesion, size of the lesion, presence of cavitation, and presence of satellite nodules. Time Previous studies have shown that nodules that are stable over a 2-year period have a high incidence of benignity.5,6 Therefore, the initial evaluation of an SPN should be an attempt to obtain older chest radiographs to assess whether there has been interval growth of the nodule. No growth of the nodule when compared with previous studies over a 2-year interval would indicate that the nodule is benign. However, growth in it of itself does not indicate malignancy, although the presence of an enlarging SPN increases the likelihood that the nodule is malignant. An increase in nodule diameter of 26% equates with a doubling in volume of the nodule.7 Calcification Calcification within a pulmonary nodule can take on several different forms. These include diffuse calcification, central calcification, lamellar calcification, chondroid (popcorn) calcification, and eccentric calcification (Table 1).2,7,8 Of these types of calcifications, diffuse, central (Fig 2), and lamellar all indicate a benign cause, and typically these cases are caused by old granulomatous disease. Chondroid calcification not only is a benign pattern of calcification but also allows the specific
Seminars in Thoracic and Cardiovascular Surgery, Vol 14, No 3 ( July), 2002: pp 261-267
261
262
Thomas E. Hartman
Figure 1. Postero-anterior (PA) chest radiograph of a 70-year-old woman. Solitary pulmonary nodule is seen in the left lower lung laterally (arrow).
diagnosis of a hamartoma to be made. The final type of calcification, eccentric calcification, is indeterminate regarding malignancy. Eccentric calcification can either be caused by benign lesions that are calcifying eccentrically or malignant lesions, which are either undergoing dystrophic calcification or engulfing a benign calcified lesion (Fig 3).
Figure 2. Thin-section computed tomography (CT) image in a 73-year-old woman. Solitary pulmonary nodule in the right lower lobe is shown to have an area of central calcification (arrow). Because of the central calcification, this nodule was considered to be benign.
only margin characterization that has significant predictive value is a spiculated margin (Fig 4). A nodule, which has evidence of spiculation extending into the surrounding lung, has a predictive value for malignancy of approximately 90%.8 Therefore, the presence of spiculation should prompt a more aggressive workup of the pulmonary nodule.8-10 The presence of a smooth border, however, does not indicate benignity, and up to
Margins Margins of the nodule may be smooth, lobulated, irregular, or spiculated. Other descriptors are sometimes used. Regardless of the descriptor, the
Table 1. Benign and Indeterminate calcification patterns.
Figure 3. Tomogram through the right lower lung in an 88-year-old woman. Lobulated solitary pulmonary nodule contains an area of eccentric calcification (arrow), making this nodule indeterminate. At resection, the nodule was shown to be an adenocarcinoma engulfing an adjacent calcified granuloma.
Solitary Pulmonary Nodule
263
Figure 5. CT image at the level of the bronchus intermedius in a 65-year-old man. There is a spiculated nodule in the right lower lobe (arrow). One of the spiculations extends to the pleural surface posteriorly. At resection, the nodule was shown to be a histoplasma granuloma. Figure 4. Tomogram through the left upper lobe of an 82-year-old man. Solitary pulmonary nodule with spiculated borders also contains a small amount of eccentric dystrophic calcification. At resection, the nodule was shown to be a squamous cell carcinoma.
21% of malignant lesions can have a smooth border.11 Therefore, nodules with smooth borders must remain indeterminate. It should also be remembered that although spiculated lesions have a 90% predictive value for malignancy, 10% of spiculated nodules will be benign (Fig 5) and therefore, spiculation by itself cannot be used as a confident discriminator between benign and malignant lesions.
thin walls, whereas malignant cavitary nodules have thick, irregular walls. The internal walls of cavitary nodules may also be helpful in discriminating benign and malignant cavitary nodules. Benign nodules tend to have smooth inner walls (Fig 6), whereas malignant nodules tend to have a nodular contour along the inner wall of the cavity. However, there is significant overlap, and the characteristics of the walls of cavitary nodules
Size The majority of pulmonary nodules, which are benign, are less than 2 cm in diameter so that lesions larger than 3 cm are more likely to be malignant than benign. However, lesion size below 2 cm does not exclude malignancy as 42% of malignant nodules are ⬍2 cm and 15% of malignant nodules are ⬍1 cm in diameter.3,8,9 Additionally, with the advent of CT for lung cancer screening, it is likely that an increasing number of lung cancers less than 1 cm will be identified. Cavitation Both benign and malignant nodules can cavitate. Typically benign cavitary nodules have smooth,
Figure 6. Localized view of a PA chest radiograph of a 25-year-old man. There is a thin-walled cavitary nodule in the right upper lung (arrows). Note the smooth inner wall in this cavitary nodule caused by coccidioidomycosis.
264
Thomas E. Hartman
cannot be used to confidently differentiate benign from malignant nodule.9,12,13 Satellite Nodules The presence of tiny nodules associated with the dominant pulmonary nodule is referred to as satellite nodules (Fig 7). The presence of satellite nodules indicates a high likelihood that the dominant nodule is benign. The positive predictive value for benignity with satellite nodules is approximately 90%.8 However, the presence of satellite nodules does not allow confident diagnosis of benignity, as 10% of dominant nodules with satellite nodules will be malignant.
CT Although the chest radiograph is useful in the initial evaluation of SPNs, CT can often provide additional information in the evaluation of SPNs. CT is more sensitive to the detection of calcification within a pulmonary nodule and, therefore, nodules, which are indeterminate in the chest radiograph, can often be further characterized and given a benign diagnosis based on the discovery of calcification at CT.9-11 In addition to being
Figure 8. Targeted CT at the level of the carina in an 82-year-old man. The pulmonary nodule in the right lower lobe shows central areas of fat (arrows) as well as a tiny area of calcification. These CT features are diagnostic of a pulmonary hamartoma.
able to better demonstrate calcification, CT is also particularly helpful in detection of fat within a pulmonary nodule (Fig 8). The presence of fat within a pulmonary nodule is an indication of benignity and is typically seen with hamartoma.14 In addition to the presence of calcification or fat, CT can also be used to better evaluate the margins, size, and cavitation of lesions. Volumetric Assessment
Figure 7. Localized CT of the left upper lung in a 42-year-old woman. There are 3 tiny satellite nodules (arrows) adjacent to the dominant nodule in the left upper lung. This nodule was observed for over 2 years without evidence of interval growth, confirming that it was benign.
The growth rate of a pulmonary nodule has been previously discussed using diameter measurements. However, additional measurement tools are now becoming available on CT, which will allow volumetric assessment of the nodule.15 This allows a more accurate determination of the doubling time of the nodule on images taken in as short a time as 1 month apart. The doubling time for most malignant nodules is between 30 and 400 days. Lack of significant growth over a 2-year period implies a doubling time of at least 730 days, and this is generally considered to be benign. There are currently a number of systems in development, and volumetric assessment will
Solitary Pulmonary Nodule
265
likely play an increasingly important role in the evaluation of indeterminate pulmonary nodules in the future. Nodule Enhancement An additional test that can be performed with CT includes contrast enhancement of the pulmonary nodule. The reason for this is that blood flow in malignant pulmonary nodules is increased compared with benign pulmonary nodules. The degree of enhancement is directly related to the vascularity of the nodule, and this is increased in malignancy.16-17 Contrast material is administered intravenously, and the attenuation of the nodule is measured every 60 seconds for 4 minutes and compared with the attenuation measurement of the nodule taken before the injection of contrast (Fig 9). Nodule enhancement of less than 15 Hounsfield units after administration of contrast material is strongly predictive of benignity (positive predictive value for benignity of 99%). However, only 58% of nodules with enhancement of greater than 15 Hounsfield units will be malignant.18 Therefore, enhancing nodules, while more likely to be malignant, are still indeterminate and will require further workup to establish a diagnosis. CT enhancement studies have additional limitations. Lesions less than 8 mm in diameter, cavitary lesions, and lesions with central necrosis are not amenable to CT enhancement studies.16-18
Positron Emission Tomography Positron emission tomography (PET) is an imaging technique that uses metabolic substrates labeled with positron-emitting isotopes. The most commonly used radionuclide is a glucose analog, 18Fluoro-2-deoxyglucose (FDG). Increased glucose metabolism in tumors relative to benign nodules results in increased uptake and accumulation of FDG, permitting differentiation of benign and malignant nodules. The sensitivity, specificity, and accuracy of PET in the diagnosis of benign nodules have been shown to be 90% or greater in several studies.19-21 The high specificity of PET for the diagnosis of benign lesions has important clinical utility in that lesions with low FDG uptake may be considered benign. However, there are instances with slow-growing malignancies such as bronchioloalveolar carcinoma where false-negatives can occur. Therefore, lesions that are FDG negative
Figure 9. Localized CT images through a pulmonary nodule in a 60-year-old woman. (A) Region of interest is drawn within the pulmonary nodule on this precontrast scan. The measurement before contrast was 11 Hounsfield units. (B) Region of interest drawn in the pulmonary nodule after the injection of intravenous contrast. The measurement at this time was 74 Hounsfield units. The difference of 63 Hounsfield units indicates a higher likelihood that the nodule is malignant. At resection, the nodule was shown to be an adenocarcinoma.
should continue to be followed up radiographically to ensure that there is no interval growth. Another limitation is that PET typically has difficulty accurately evaluating lesions that are less than 10 mm in diameter.22-23 Finally, PET can yield false-positives in patients with active infectious or inflammatory processes such as tuberculosis and histoplasmosis (Fig 10).24 Transthoracic Needle Aspiration When the radiologic features of a pulmonary nodule are not diagnostic, transthoracic needle aspi-
266
Thomas E. Hartman
orrhage is almost always self-limiting, although it can occasionally be life threatening. Bayesian Analysis Bayesian analysis can be useful in the evaluation of the indeterminate SPN. Bayesian analysis uses likelihood ratios of numerous radiologic findings and clinical features associated with SPNs to estimate the probability of malignancy.8,29 In addition to some of the radiologic findings discussed previously, age and smoking history are factors that are included in bayesian analysis. The mathematics of bayesian analysis are beyond the scope of this article, but it has been shown that bayesian analysis is equivalent or slightly superior to the evaluation of an experienced radiologist in the stratification of benign and malignant pulmonary nodules.8
Figure 10. Positron emission tomography (PET) image from a 36-year-old woman. There is increased uptake in the left upper lung (arrow) corresponding to a nodule seen on a chest radiograph. At the time of resection, the nodule was shown to be a histoplasma granuloma.
ration (TTNA) can be an effective tool in diagnosing pulmonary nodule.25-27 Transthoracic needle aspiration is optimally used in peripheral nodules, although biopsies can be performed on more central lesions (Fig 11). TTNA has a high sensitivity for the diagnosis of malignancy even in small nodules, but it can sometimes be difficult to establish a specific benign diagnosis. However, the exclusion of malignancy even without arriving at a specific benign diagnosis may be clinically useful and allow a lesion to be monitored radiologically rather than progressing to more aggressive intervention. In addition to difficulties making specific benign diagnoses, there are complications associated with transthoracic needle aspirations. The most common are pneumothorax and hemorrhage.25,28 Pneumothorax occurs in 5% to 30% of patients but is typically not clinically significant, and only about 15% of patients with a pneumothorax will eventually require chest tubes. Hem-
Figure 11. Localized CT shows a small pulmonary nodule in the left lower lobe. The tip of a transthoracic needle is seen along the anterolateral margin of the nodule (arrow). Findings at transthoracic needle aspiration were positive for malignancy, and at resection the nodule was shown to be an adenocarcinoma.
Solitary Pulmonary Nodule
Conclusion The SPN is a common radiologic finding. The advent of low-dose screening chest CT will increase the likelihood that these lesions will need to be dealt with in the future. There is no single correct management approach, and the workup can often require extensive evaluation to establish a benign or malignant diagnosis. Comparison with old examinations and morphologic evaluation of the size, margins, and internal characteristics of a solitary pulmonary nodule should be the first step in the evaluation of these lesions. However, it will often be necessary to proceed to additional imaging techniques such as CT or PET, and in some situations further invasive tests such as TTNA may be required.
References 1. Lillington GA: Disease a Month (ed 47). St. Louis, MO, Mosby Yearbook, 1991, pp 271-318 2. Midthun DE, Swensen SJ, Jett JR: Approach to the solitary pulmonary nodule. Mayo Clin Proc 68:378-385, 1993 3. Higgins GA, Shield TW, Keehn RJ: The solitary pulmonary nodule. Arch Surg 110:570-575, 1975 4. Gomstock GW, Vaughan RH, Montgomery G: Outcome of solitary pulmonary nodules discovered in an x-ray screening program. N Engl J Med 254:1018-1022, 1956 5. Good CA, Wilson TW: The solitary circumscribed pulmonary nodule. JAMA 166:210-215, 1958 6. Hood RT Jr, Good CA, Clagett OT, et al: Solitary circumscribed lesions of the lung: Study of a 156 cases in which resection was performed. JAMA 152:1185-1191, 1953 7. Lillington GA, Caskey CE: Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 14:111-119, 1993 8. Gurney JW: Determining the likelihood of malignancy in solitary pulmonary nodules with bayesian analysis. Radiology 186:405-413, 1993 9. Zwirewich CV, Vedal S, Miller RR, Mu ¨eller NL: Solitary pulmonary nodule: High resolution CT and radiologic/ pathologic correlation. Radiology 179:469-476, 1991 10. Zerhouni EA, Stitik FP, Siegelman SS, et al: CT of the pulmonary nodule: A cooperative study. Radiology 160: 319-327, 1986 11. Siegelman SS, Zerhouni EA, Leo FP, et al: CT of the solitary pulmonary nodule. AJR Am J Roentgenol 135:113, 1980
267
12. Theros EG: Varying manifestations of peripheral pulmonary neoplasms: A radiologic/pathologic correlative study. AJR Am J Roentgenol 128:893-914, 1977 13. Woodring JH, Fried AM, Chuang VP: Solitary cavities of the lung: Diagnostic implications of cavitary wall thickness. AJR Am J Roentgenol 135:1269-1271, 1980 14. Siegelman SS, Khouri NF, Scott WW Jr, et al: Pulmonary hamartoma: CT findings. Radiology 160:313-317, 1986 15. Yankelevitz DF, Reeves AP, Kostis WJ, et al: Small pulmonary nodules: Volumetrically determined growth rates based on CT evaluation. Radiology 217:251-256, 2000 16. Swensen SJ, Brown LR, Colby TV, et al: Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material. Radiology 194:393-398, 1995 17. Swensen SJ, Brown LR, Colby TV, et al: Lung nodule enhancement at CT: Prospective findings. Radiology 201: 447-455, 1996 18. Swensen SJ, Vigianno RW, Midthun JE, et al: Lung nodule enhancement at CT: Multicenter study. Radiology 214:73-80, 2000 19. Patz EF, Lowe VJ, Hoffman JM, et al: Focal pulmonary abnormalities: Evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 188:487-490, 1993 20. Gupta NC, Frank AR, Dewan NA, et al: Solitary pulmonary nodules: Detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 184:441444, 1992 21. Gupta NC, Maloof J, Gunel E: Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 37:943-948, 1996 22. Erasmus JJ, McAdams HP, Patz EF, et al: Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 170:1369-1373, 1998 23. Higashi K, Ueda Y, Seki H, et al: Fluorine 18 FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 39:1016-1020, 1998 24. Lowe VJ, Fletcher JW, Gobar L: Prospective investigation of PET and lung nodules (PIOPILN). J Clin Oncol 16: 1075-1084, 1998 25. Kline JS, Zarka MA: Thoracic needle biopsy: an overview. J Thorac Imaging 12:232-249, 1997 26. Westcott JL, Rao N, Colly DP: Transthoracic needle biopsy of pulmonary nodules. Radiology 202:97-103, 1997 27. Li H, Boiselle PM, Shepard JO, et al: Diagnostic accuracy and safety of CT guided percutaneous needle aspiration biopsy of the lung. Comparison of small and large pulmonary nodules. AJR Am J Roentgenol 167:105-109, 1996 28. Moore EH: Needle aspiration lung biopsy: A comprehensive approach to complication reduction. J Thorac Imaging 12:259-271, 1997 29. Black WC, Armstrong P: Communicating the significance of radiologic test results: The likelihood ratio. AJR Am J Roentgenol 147:1313-1318, 1986.
S
olitary pulmonary nodules (SPN) are round or oval areas of increased opacity in the lung on a chest radiograph that measure less than 3 cm in diameter. These nodules can be caused by a variety of disorders including neoplasms, infection, inflammation, and vascular and congenital abnormalities. In 1991, it was estimated that approximately 150,000 solitary pulmonary nodules were detected in the United States annually.1 Many of these are discovered incidentally at chest radiography (Fig 1) or computed tomography (CT). Although most SPNs are benign, up to 40% of these nodules may be malignant.2-4 With the advent of low-dose screening for lung cancer, the incidence of solitary pulmonary nodules, which requires further evaluation, is likely to increase.
Chest Radiograph Standard radiologic evaluation of pulmonary nodules on the chest radiograph has the primary function of trying to differentiate benign from malignant lesions. There are certain imaging criteria on the chest radiograph or CT that can be used to predict the likelihood of a nodule being benign or malignant. The two primary criteria for From the Department of Radiology, Mayo Clinic, Rochester, MN. Address reprint requests to Thomas E. Hartman, MD, Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Copyright 2002, Elsevier Science (USA). All rights reserved. 1043-0679/02/1403-0000$35.00/0 doi:10.1053/stcs.2002.33155
the evaluation of SPNs are time and calcification within the nodule. Other criteria that may be helpful include margins of the lesion, size of the lesion, presence of cavitation, and presence of satellite nodules. Time Previous studies have shown that nodules that are stable over a 2-year period have a high incidence of benignity.5,6 Therefore, the initial evaluation of an SPN should be an attempt to obtain older chest radiographs to assess whether there has been interval growth of the nodule. No growth of the nodule when compared with previous studies over a 2-year interval would indicate that the nodule is benign. However, growth in it of itself does not indicate malignancy, although the presence of an enlarging SPN increases the likelihood that the nodule is malignant. An increase in nodule diameter of 26% equates with a doubling in volume of the nodule.7 Calcification Calcification within a pulmonary nodule can take on several different forms. These include diffuse calcification, central calcification, lamellar calcification, chondroid (popcorn) calcification, and eccentric calcification (Table 1).2,7,8 Of these types of calcifications, diffuse, central (Fig 2), and lamellar all indicate a benign cause, and typically these cases are caused by old granulomatous disease. Chondroid calcification not only is a benign pattern of calcification but also allows the specific
Seminars in Thoracic and Cardiovascular Surgery, Vol 14, No 3 ( July), 2002: pp 261-267
261
262
Thomas E. Hartman
Figure 1. Postero-anterior (PA) chest radiograph of a 70-year-old woman. Solitary pulmonary nodule is seen in the left lower lung laterally (arrow).
diagnosis of a hamartoma to be made. The final type of calcification, eccentric calcification, is indeterminate regarding malignancy. Eccentric calcification can either be caused by benign lesions that are calcifying eccentrically or malignant lesions, which are either undergoing dystrophic calcification or engulfing a benign calcified lesion (Fig 3).
Figure 2. Thin-section computed tomography (CT) image in a 73-year-old woman. Solitary pulmonary nodule in the right lower lobe is shown to have an area of central calcification (arrow). Because of the central calcification, this nodule was considered to be benign.
only margin characterization that has significant predictive value is a spiculated margin (Fig 4). A nodule, which has evidence of spiculation extending into the surrounding lung, has a predictive value for malignancy of approximately 90%.8 Therefore, the presence of spiculation should prompt a more aggressive workup of the pulmonary nodule.8-10 The presence of a smooth border, however, does not indicate benignity, and up to
Margins Margins of the nodule may be smooth, lobulated, irregular, or spiculated. Other descriptors are sometimes used. Regardless of the descriptor, the
Table 1. Benign and Indeterminate calcification patterns.
Figure 3. Tomogram through the right lower lung in an 88-year-old woman. Lobulated solitary pulmonary nodule contains an area of eccentric calcification (arrow), making this nodule indeterminate. At resection, the nodule was shown to be an adenocarcinoma engulfing an adjacent calcified granuloma.
Solitary Pulmonary Nodule
263
Figure 5. CT image at the level of the bronchus intermedius in a 65-year-old man. There is a spiculated nodule in the right lower lobe (arrow). One of the spiculations extends to the pleural surface posteriorly. At resection, the nodule was shown to be a histoplasma granuloma. Figure 4. Tomogram through the left upper lobe of an 82-year-old man. Solitary pulmonary nodule with spiculated borders also contains a small amount of eccentric dystrophic calcification. At resection, the nodule was shown to be a squamous cell carcinoma.
21% of malignant lesions can have a smooth border.11 Therefore, nodules with smooth borders must remain indeterminate. It should also be remembered that although spiculated lesions have a 90% predictive value for malignancy, 10% of spiculated nodules will be benign (Fig 5) and therefore, spiculation by itself cannot be used as a confident discriminator between benign and malignant lesions.
thin walls, whereas malignant cavitary nodules have thick, irregular walls. The internal walls of cavitary nodules may also be helpful in discriminating benign and malignant cavitary nodules. Benign nodules tend to have smooth inner walls (Fig 6), whereas malignant nodules tend to have a nodular contour along the inner wall of the cavity. However, there is significant overlap, and the characteristics of the walls of cavitary nodules
Size The majority of pulmonary nodules, which are benign, are less than 2 cm in diameter so that lesions larger than 3 cm are more likely to be malignant than benign. However, lesion size below 2 cm does not exclude malignancy as 42% of malignant nodules are ⬍2 cm and 15% of malignant nodules are ⬍1 cm in diameter.3,8,9 Additionally, with the advent of CT for lung cancer screening, it is likely that an increasing number of lung cancers less than 1 cm will be identified. Cavitation Both benign and malignant nodules can cavitate. Typically benign cavitary nodules have smooth,
Figure 6. Localized view of a PA chest radiograph of a 25-year-old man. There is a thin-walled cavitary nodule in the right upper lung (arrows). Note the smooth inner wall in this cavitary nodule caused by coccidioidomycosis.
264
Thomas E. Hartman
cannot be used to confidently differentiate benign from malignant nodule.9,12,13 Satellite Nodules The presence of tiny nodules associated with the dominant pulmonary nodule is referred to as satellite nodules (Fig 7). The presence of satellite nodules indicates a high likelihood that the dominant nodule is benign. The positive predictive value for benignity with satellite nodules is approximately 90%.8 However, the presence of satellite nodules does not allow confident diagnosis of benignity, as 10% of dominant nodules with satellite nodules will be malignant.
CT Although the chest radiograph is useful in the initial evaluation of SPNs, CT can often provide additional information in the evaluation of SPNs. CT is more sensitive to the detection of calcification within a pulmonary nodule and, therefore, nodules, which are indeterminate in the chest radiograph, can often be further characterized and given a benign diagnosis based on the discovery of calcification at CT.9-11 In addition to being
Figure 8. Targeted CT at the level of the carina in an 82-year-old man. The pulmonary nodule in the right lower lobe shows central areas of fat (arrows) as well as a tiny area of calcification. These CT features are diagnostic of a pulmonary hamartoma.
able to better demonstrate calcification, CT is also particularly helpful in detection of fat within a pulmonary nodule (Fig 8). The presence of fat within a pulmonary nodule is an indication of benignity and is typically seen with hamartoma.14 In addition to the presence of calcification or fat, CT can also be used to better evaluate the margins, size, and cavitation of lesions. Volumetric Assessment
Figure 7. Localized CT of the left upper lung in a 42-year-old woman. There are 3 tiny satellite nodules (arrows) adjacent to the dominant nodule in the left upper lung. This nodule was observed for over 2 years without evidence of interval growth, confirming that it was benign.
The growth rate of a pulmonary nodule has been previously discussed using diameter measurements. However, additional measurement tools are now becoming available on CT, which will allow volumetric assessment of the nodule.15 This allows a more accurate determination of the doubling time of the nodule on images taken in as short a time as 1 month apart. The doubling time for most malignant nodules is between 30 and 400 days. Lack of significant growth over a 2-year period implies a doubling time of at least 730 days, and this is generally considered to be benign. There are currently a number of systems in development, and volumetric assessment will
Solitary Pulmonary Nodule
265
likely play an increasingly important role in the evaluation of indeterminate pulmonary nodules in the future. Nodule Enhancement An additional test that can be performed with CT includes contrast enhancement of the pulmonary nodule. The reason for this is that blood flow in malignant pulmonary nodules is increased compared with benign pulmonary nodules. The degree of enhancement is directly related to the vascularity of the nodule, and this is increased in malignancy.16-17 Contrast material is administered intravenously, and the attenuation of the nodule is measured every 60 seconds for 4 minutes and compared with the attenuation measurement of the nodule taken before the injection of contrast (Fig 9). Nodule enhancement of less than 15 Hounsfield units after administration of contrast material is strongly predictive of benignity (positive predictive value for benignity of 99%). However, only 58% of nodules with enhancement of greater than 15 Hounsfield units will be malignant.18 Therefore, enhancing nodules, while more likely to be malignant, are still indeterminate and will require further workup to establish a diagnosis. CT enhancement studies have additional limitations. Lesions less than 8 mm in diameter, cavitary lesions, and lesions with central necrosis are not amenable to CT enhancement studies.16-18
Positron Emission Tomography Positron emission tomography (PET) is an imaging technique that uses metabolic substrates labeled with positron-emitting isotopes. The most commonly used radionuclide is a glucose analog, 18Fluoro-2-deoxyglucose (FDG). Increased glucose metabolism in tumors relative to benign nodules results in increased uptake and accumulation of FDG, permitting differentiation of benign and malignant nodules. The sensitivity, specificity, and accuracy of PET in the diagnosis of benign nodules have been shown to be 90% or greater in several studies.19-21 The high specificity of PET for the diagnosis of benign lesions has important clinical utility in that lesions with low FDG uptake may be considered benign. However, there are instances with slow-growing malignancies such as bronchioloalveolar carcinoma where false-negatives can occur. Therefore, lesions that are FDG negative
Figure 9. Localized CT images through a pulmonary nodule in a 60-year-old woman. (A) Region of interest is drawn within the pulmonary nodule on this precontrast scan. The measurement before contrast was 11 Hounsfield units. (B) Region of interest drawn in the pulmonary nodule after the injection of intravenous contrast. The measurement at this time was 74 Hounsfield units. The difference of 63 Hounsfield units indicates a higher likelihood that the nodule is malignant. At resection, the nodule was shown to be an adenocarcinoma.
should continue to be followed up radiographically to ensure that there is no interval growth. Another limitation is that PET typically has difficulty accurately evaluating lesions that are less than 10 mm in diameter.22-23 Finally, PET can yield false-positives in patients with active infectious or inflammatory processes such as tuberculosis and histoplasmosis (Fig 10).24 Transthoracic Needle Aspiration When the radiologic features of a pulmonary nodule are not diagnostic, transthoracic needle aspi-
266
Thomas E. Hartman
orrhage is almost always self-limiting, although it can occasionally be life threatening. Bayesian Analysis Bayesian analysis can be useful in the evaluation of the indeterminate SPN. Bayesian analysis uses likelihood ratios of numerous radiologic findings and clinical features associated with SPNs to estimate the probability of malignancy.8,29 In addition to some of the radiologic findings discussed previously, age and smoking history are factors that are included in bayesian analysis. The mathematics of bayesian analysis are beyond the scope of this article, but it has been shown that bayesian analysis is equivalent or slightly superior to the evaluation of an experienced radiologist in the stratification of benign and malignant pulmonary nodules.8
Figure 10. Positron emission tomography (PET) image from a 36-year-old woman. There is increased uptake in the left upper lung (arrow) corresponding to a nodule seen on a chest radiograph. At the time of resection, the nodule was shown to be a histoplasma granuloma.
ration (TTNA) can be an effective tool in diagnosing pulmonary nodule.25-27 Transthoracic needle aspiration is optimally used in peripheral nodules, although biopsies can be performed on more central lesions (Fig 11). TTNA has a high sensitivity for the diagnosis of malignancy even in small nodules, but it can sometimes be difficult to establish a specific benign diagnosis. However, the exclusion of malignancy even without arriving at a specific benign diagnosis may be clinically useful and allow a lesion to be monitored radiologically rather than progressing to more aggressive intervention. In addition to difficulties making specific benign diagnoses, there are complications associated with transthoracic needle aspirations. The most common are pneumothorax and hemorrhage.25,28 Pneumothorax occurs in 5% to 30% of patients but is typically not clinically significant, and only about 15% of patients with a pneumothorax will eventually require chest tubes. Hem-
Figure 11. Localized CT shows a small pulmonary nodule in the left lower lobe. The tip of a transthoracic needle is seen along the anterolateral margin of the nodule (arrow). Findings at transthoracic needle aspiration were positive for malignancy, and at resection the nodule was shown to be an adenocarcinoma.
Solitary Pulmonary Nodule
Conclusion The SPN is a common radiologic finding. The advent of low-dose screening chest CT will increase the likelihood that these lesions will need to be dealt with in the future. There is no single correct management approach, and the workup can often require extensive evaluation to establish a benign or malignant diagnosis. Comparison with old examinations and morphologic evaluation of the size, margins, and internal characteristics of a solitary pulmonary nodule should be the first step in the evaluation of these lesions. However, it will often be necessary to proceed to additional imaging techniques such as CT or PET, and in some situations further invasive tests such as TTNA may be required.
References 1. Lillington GA: Disease a Month (ed 47). St. Louis, MO, Mosby Yearbook, 1991, pp 271-318 2. Midthun DE, Swensen SJ, Jett JR: Approach to the solitary pulmonary nodule. Mayo Clin Proc 68:378-385, 1993 3. Higgins GA, Shield TW, Keehn RJ: The solitary pulmonary nodule. Arch Surg 110:570-575, 1975 4. Gomstock GW, Vaughan RH, Montgomery G: Outcome of solitary pulmonary nodules discovered in an x-ray screening program. N Engl J Med 254:1018-1022, 1956 5. Good CA, Wilson TW: The solitary circumscribed pulmonary nodule. JAMA 166:210-215, 1958 6. Hood RT Jr, Good CA, Clagett OT, et al: Solitary circumscribed lesions of the lung: Study of a 156 cases in which resection was performed. JAMA 152:1185-1191, 1953 7. Lillington GA, Caskey CE: Evaluation and management of solitary and multiple pulmonary nodules. Clin Chest Med 14:111-119, 1993 8. Gurney JW: Determining the likelihood of malignancy in solitary pulmonary nodules with bayesian analysis. Radiology 186:405-413, 1993 9. Zwirewich CV, Vedal S, Miller RR, Mu ¨eller NL: Solitary pulmonary nodule: High resolution CT and radiologic/ pathologic correlation. Radiology 179:469-476, 1991 10. Zerhouni EA, Stitik FP, Siegelman SS, et al: CT of the pulmonary nodule: A cooperative study. Radiology 160: 319-327, 1986 11. Siegelman SS, Zerhouni EA, Leo FP, et al: CT of the solitary pulmonary nodule. AJR Am J Roentgenol 135:113, 1980
267
12. Theros EG: Varying manifestations of peripheral pulmonary neoplasms: A radiologic/pathologic correlative study. AJR Am J Roentgenol 128:893-914, 1977 13. Woodring JH, Fried AM, Chuang VP: Solitary cavities of the lung: Diagnostic implications of cavitary wall thickness. AJR Am J Roentgenol 135:1269-1271, 1980 14. Siegelman SS, Khouri NF, Scott WW Jr, et al: Pulmonary hamartoma: CT findings. Radiology 160:313-317, 1986 15. Yankelevitz DF, Reeves AP, Kostis WJ, et al: Small pulmonary nodules: Volumetrically determined growth rates based on CT evaluation. Radiology 217:251-256, 2000 16. Swensen SJ, Brown LR, Colby TV, et al: Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material. Radiology 194:393-398, 1995 17. Swensen SJ, Brown LR, Colby TV, et al: Lung nodule enhancement at CT: Prospective findings. Radiology 201: 447-455, 1996 18. Swensen SJ, Vigianno RW, Midthun JE, et al: Lung nodule enhancement at CT: Multicenter study. Radiology 214:73-80, 2000 19. Patz EF, Lowe VJ, Hoffman JM, et al: Focal pulmonary abnormalities: Evaluation with F-18 fluorodeoxyglucose PET scanning. Radiology 188:487-490, 1993 20. Gupta NC, Frank AR, Dewan NA, et al: Solitary pulmonary nodules: Detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 184:441444, 1992 21. Gupta NC, Maloof J, Gunel E: Probability of malignancy in solitary pulmonary nodules using fluorine-18-FDG and PET. J Nucl Med 37:943-948, 1996 22. Erasmus JJ, McAdams HP, Patz EF, et al: Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 170:1369-1373, 1998 23. Higashi K, Ueda Y, Seki H, et al: Fluorine 18 FDG PET imaging is negative in bronchioloalveolar lung carcinoma. J Nucl Med 39:1016-1020, 1998 24. Lowe VJ, Fletcher JW, Gobar L: Prospective investigation of PET and lung nodules (PIOPILN). J Clin Oncol 16: 1075-1084, 1998 25. Kline JS, Zarka MA: Thoracic needle biopsy: an overview. J Thorac Imaging 12:232-249, 1997 26. Westcott JL, Rao N, Colly DP: Transthoracic needle biopsy of pulmonary nodules. Radiology 202:97-103, 1997 27. Li H, Boiselle PM, Shepard JO, et al: Diagnostic accuracy and safety of CT guided percutaneous needle aspiration biopsy of the lung. Comparison of small and large pulmonary nodules. AJR Am J Roentgenol 167:105-109, 1996 28. Moore EH: Needle aspiration lung biopsy: A comprehensive approach to complication reduction. J Thorac Imaging 12:259-271, 1997 29. Black WC, Armstrong P: Communicating the significance of radiologic test results: The likelihood ratio. AJR Am J Roentgenol 147:1313-1318, 1986.