Journal of Thoracic Imaging:
Web Exclusive Content-ACR Appropriateness Criteria(R) Review
ACR Appropriateness Criteria® Radiographically Detected Solitary Pulmonary Nodule
Kanne, Jeffrey P. MD*; Jensen, Leif E. MD, MPH*; Mohammed, Tan-Lucien H. MD†; Kirsch, Jacobo MD‡; Amorosa, Judith K. MD§; Brown, Kathleen MD∥; Chung, Jonathan H. MD¶; Dyer, Debra Sue MD¶; Ginsburg, Mark E. MD#; Heitkamp, Darel E. MD**; Kazerooni, Ella A. MD††; Ketai, Loren H. MD‡‡; Parker, J. Anthony MD, PhD§§; Ravenel, James G. MD∥∥; Saleh, Anthony G. MD¶¶; Shah, Rakesh D. MD##; Expert Panel on Thoracic Imaging
*Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI
†Cleveland Clinic Foundation, Cleveland, OH
‡Cleveland Clinic, Weston, FL
§Robert Wood Johnson Medical School, New Brunswick, NJ
∥Ronald Regan UCLA Medical Center, Los Angeles, CA
¶National Jewish Health, Denver, CO
#Department of Surgery, Society of Thoracic Surgeons, Columbia University, New York, NY
¶¶The American College of Chest Physicians, New York Methodist Hospital, Brooklyn, NY
##Department of Radiology, North Shore University Hospital, Manhasset, NY
**Department of Radiology, Indiana University, Indianapolis, IN
††Department of Radiology, University of Michigan Medical Center, Ann Arbor, MI
‡‡Department of Radiology, University of New Mexico, Albuquerque, NM
§§Society of Nuclear Medicine, Beth Israel Deaconess Medical Center, Boston, MA
∥∥Department of Radiology, Medical University of South Carolina, Charleston, SC
Jeffrey P. Kanne is a consultant for PTC Therapeutics ($13,000) not relevant to ACR activities or imaging. For the remaining authors none were declared.
The American College of Radiology (ACR) seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria® through society representation on expert panels. Participation by representatives from collaborating societies on the expert panel does not necessarily imply individual or society endorsement of the final document.
This article is a revised version of the American College of Radiology Appropriateness Criteria® Radiographically Detected Solitary Pulmonary Nodule. Practitioners are encouraged to refer to the complete version at http://www.acr.org/ac.
Reprints: Jeffrey P. Kanne, MD, American College of Radiology, 1891 Preston White Drive, Reston, VA 20191 (e-mail: email@example.com).
The solitary pulmonary nodule (SPN) is a common medical problem for which management can be quite complex. Imaging remains at the center of management of SPNs, and computed tomography is the primary modality by which SPNs are characterized and followed up for stability. This manuscript summarizes the American College of Radiology Appropriateness Criteria® for radiographically detected solitary pulmonary nodules and briefly reviews the various imaging techniques available. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
SUMMARY OF LITERATURE REVIEW
The solitary pulmonary nodule is defined as a rounded opacity ≤3 cm in diameter surrounded by lung parenchyma.1 There should be no associated abnormality, including atelectasis or hilar lymphadenopathy. This definition is based on information obtained from chest radiographs. On computed tomography (CT), nodules are described as being solid, semisolid (mixed attenuation), or ground-glass attenuation. Pure ground-glass attenuation nodules are areas of increased lung attenuation through which normal structures such as vessels or septa remain discernible.
The incidence of solitary nodules detected by chest radiography was previously estimated to be approximately 150,000 per year in the United States.2 However, this figure did not include the multitude of smaller nodules detected with CT. There are few reliable characteristics to distinguish benign from malignant nodules. The only findings sufficient to preclude further evaluation are a benign pattern of calcification or stability of nodule size for over 2 years for solid pulmonary nodules. Recently, the radiologic-pathologic correlation of pure ground-glass attenuation nodules and mixed attenuation nodules with the histologic spectrum of pulmonary adenocarcinoma was described.3 Although not all ground-glass attenuation nodules are malignant, they are more likely to be multiple and may demonstrate an indolent growth pattern, rendering 2-year stability inadequate to establish benignity. The likelihood of malignancy increases with nodule size, which may influence management strategy. Other nodule features such as shape, edge characteristics, cavitation, and location have not yet been found to be accurate clues for distinguishing benign from malignant nodules.4
OVERVIEW OF DIAGNOSTIC TESTS
A host of diagnostic tests are available to evaluate patients with solitary pulmonary nodules (Table 1). It should be noted that for all of these tests accuracy tends to decrease with decreasing nodule size. It is often the role of the radiologist to suggest an appropriate management strategy.
Theoretical approaches for decision-making include the use of Bayes theorem, logistic regression models, and neural network analysis.5–8 These approaches are useful primarily in estimating the probability of malignancy for a particular nodule. Information from the radiologic appearance of the nodule, such as size, shape, and edge characteristics, can be combined with clinical risk information such as age and smoking history to produce an overall probability for malignancy. If this probability can be set sufficiently low, strategies that include observing nodules for interval change can be advocated.9 These estimates can be combined with subsequent imaging information to further define the probability of malignancy and guide additional steps in the diagnostic workup.10
Extensive work is now being done using advanced image processing techniques to further evaluate nodule attributes and change over time. Volumetric analysis measures growth of nodules in short time intervals, allowing for assessment of doubling time, which is a biological measure of tumor aggressiveness. Changes in nodule morphology and attenuation are also being assessed.11 Factors that affect the reproducibility of nodule volume measurement on CT include nodule size at detection, examination technique, nodule relationship to adjacent structures, underlying lung disease, and patient factors such as phase of respiration and cardiac motion.12
Contrast-enhanced CT of solitary pulmonary nodules has also been used to distinguish benign from malignant nodules. Results from a large multicenter study found that contrast-enhanced CT has a sensitivity of 98% and a specificity of 58% when using a cutoff of 15 Hounsfield units for enhancement. This led the authors to conclude that absence of enhancement is a strong predictor of benignity.13 An analysis of combined wash-in and washout characteristics on dynamic contrast-enhanced multidetector CT showed 92% accuracy for distinguishing benign from malignant nodules.14 Limitations of the technique relate to its nonspecific nature for inflammatory disease and measurement error in evaluation of small nodules. Dual-energy CT imaging has also been used in several studies to evaluate nodules with similar diagnostic accuracy.15,16
MAGNETIC RESONANCE IMAGING (MRI)
Use of MRI in the evaluation of pulmonary nodules has thus far been limited. Faster imaging sequences and techniques to mitigate artefacts have allowed for detection of smaller nodules (6 to 10 mm) with a sensitivity of almost 95%.17 For nodules >1 cm, contrast-enhanced dynamic MRI has been shown to be comparable to CT for distinguishing benign from malignant nodules.18–20 However, further research and validation are required to define a place for MRI in clinical practice.
POSITRON EMISSION TOMOGRAPHY (PET)
PET using fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) has assumed a major role in the evaluation of patients with solitary pulmonary nodules. Many studies have demonstrated the accuracy of FDG-PET in evaluating solitary pulmonary nodules.21 The sensitivity and specificity of this technique range from 83% to 97% and from 69% to 100%, respectively. FDG-PET has a higher specificity and only slightly reduced sensitivity compared with nodule-enhancement CT.22 Limitations of PET scanning include its inability to accurately characterize certain types of lesions, including low-grade adenocarcinoma and typical carcinoid tumors. It is also limited in its ability to characterize nodules <1 cm in diameter, and it may give false-positive results in patients with active infections and inflammatory diseases.
OTHER DIAGNOSTIC TESTS
The aggressive nature of lung cancer often compels the diagnostic evaluation to be nearly accurate, and consequently tests that provide pathologic material are quite useful. Currently, such diagnostic tests include transthoracic needle biopsy (TNB), bronchoscopy, video-assisted thoracoscopic surgery (VATS), and thoracotomy. The relative roles of these procedures are not well defined in the existing literature. Both TNB23–26 and bronchoscopy27 are highly dependent on nodule size and location and on the skill of the person performing the procedure. In general, TNB has a higher sensitivity and specificity compared with bronchoscopy.
Management recommendations for small nodules were revised by the Fleischner Society in 2005 using separate algorithms for high-risk and low-risk patients.28 The American College of Chest Physicians published a set of 29 recommendations for the evaluation and management of small nodules; these recommendations stress the importance of including patient preference in management decisions.29
In view of the variety of diagnostic tests available and the variable accuracy of the different diagnostic techniques, such as FDG-PET and TNB, no single algorithm for workup is generally accepted.
Practices differ from institution to institution, likely because of the varying prevalence of lung disease in different parts of the country, varying skill levels of operators, and varying availability of equipment.
1. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008;246:697–722
2. Lillington GA Disease-a-Month. 199137th ed St Louis, Mo Mosby-Year Book:271–318
3. Godoy MC, Naidich DP. Subsolid pulmonary nodules and the spectrum of peripheral adenocarcinomas of the lung: recommended interim guidelines for assessment and management. Radiology. 2009;253:606–622
4. Brandman S, Ko JP. Pulmonary nodule detection, characterization, and management with multidetector computed tomography. J Thorac Imaging. 2011;26:90–105
5. Gurney JW. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part I. Theory. Radiology. 1993;186:405–413
6. Henschke CI, Yankelevitz DF, Mateescu I, et al. Neural networks for the analysis of small pulmonary nodules. Clin Imaging. 1997;21:390–399
7. Nakamura K, Yoshida H, Engelmann R, et al. Computerized analysis of the likelihood of malignancy in solitary pulmonary nodules with use of artificial neural networks. Radiology. 2000;214:823–830
8. Swensen SJ, Silverstein MD, Ilstrup DM, et al. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med. 1997;157:849–855
9. Truong MT, Sabloff BS, Ko JP. Multidetector CT of solitary pulmonary nodules. Radiol Clin North Am. 2010;48:141–155
10. Matsuki Y, Nakamura K, Watanabe H, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. Am J Roentgenol. 2002;178:657–663
11. de Hoop B, Gietema H, van de Vorst S, et al. Pulmonary ground-glass nodules: increase in mass as an early indicator of growth. Radiology. 2010;255:199–206
12. Kostis WJ, Yankelevitz DF, Reeves AP, et al. Small pulmonary nodules: reproducibility of three-dimensional volumetric measurement and estimation of time to follow-up CT. Radiology. 2004;231:446–452
13. Swensen SJ, Viggiano RW, Midthun DE, et al. Lung nodule enhancement at CT: multicenter study. Radiology. 2000;214:73–80
14. Jeong YJ, Lee KS, Jeong SY, et al. Solitary pulmonary nodule: characterization with combined wash-in and washout features at dynamic multi-detector row CT. Radiology. 2005;237:675–683
15. Chae EJ, Song JW, Seo JB, et al. Clinical utility of dual-energy CT in the evaluation of solitary pulmonary nodules: initial experience. Radiology. 2008;249:671–681
16. Kang MJ, Park CM, Lee CH, et al. Dual-energy CT: clinical applications in various pulmonary diseases. Radiographics. 2010;30:685–698
17. Schroeder T, Ruehm SG, Debatin JF, et al. Detection of pulmonary nodules using a 2D HASTE MR sequence: comparison with MDCT. Am J Roentgenol. 2005;185:979–984
18. Kim JH, Kim HJ, Lee KH, et al. Solitary pulmonary nodules: a comparative study evaluated with contrast-enhanced dynamic MR imaging and CT. J Comput Assist Tomogr. 2004;28:766–775
19. Schaefer JF, Vollmar J, Schick F, et al. Solitary pulmonary nodules: dynamic contrast-enhanced MR imaging--perfusion differences in malignant and benign lesions. Radiology. 2004;232:544–553
20. Kono R, Fujimoto K, Terasaki H, et al. Dynamic MRI of solitary pulmonary nodules: comparison of enhancement patterns of malignant and benign small peripheral lung lesions. Am J Roentgenol. 2007;188:26–36
21. Mavi A, Lakhani P, Zhuang H, et al. Fluorodeoxyglucose-PET in characterizing solitary pulmonary nodules, assessing pleural diseases, and the initial staging, restaging, therapy planning, and monitoring response of lung cancer. Radiol Clin North Am. 2005;43:1–21 ix
22. Christensen JA, Nathan MA, Mullan BP, et al. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. Am J Roentgenol. 2006;187:1361–1367
23. Geraghty PR, Kee ST, McFarlane G, et al. CT-guided transthoracic needle aspiration biopsy of pulmonary nodules: needle size and pneumothorax rate. Radiology. 2003;229:475–481
24. Wallace MJ, Krishnamurthy S, Broemeling LD, et al. CT-guided percutaneous fine-needle aspiration biopsy of small (<or=1-cm) pulmonary lesions. Radiology. 2002;225:823–828
25. Westcott JLTavares J, Ferruci J. Needle biopsy of the chest. Imaging-Diagnosis-Intervention. 1993 Philadelphia, PA Lippincott:1–3
26. Yankelevitz DF, Wisnivesky JP, Henschke CI. Comparison of biopsy techniques in assessment of solitary pulmonary nodules. Semin Ultrasound CT MR. 2000;21:139–148
27. Baaklini WA, Reinoso MA, Gorin AB, et al. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049–1054
28. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology. 2005;237:395–400
29. Gould MK, Fletcher J, Iannettoni MD, et al. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132(suppl):108S–130S
appropriateness criteria; pulmonary nodule; computerized tomography; positron emission tomography; biopsy
© 2013 Lippincott Williams & Wilkins, Inc.
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