Abstract
The widespread utilization of chest CT scans has increased the importance of the proper evaluation of incidentally found lung nodules. The primary goal in the evaluation of these nodules is to determine whether they are malignant or benign. Clinical factors such as older age, tobacco smoking, and current or remote history of malignancy increase the pretest likelihood of malignancy. Radiological features of these nodules are important in differentiating benign from malignant lesions. However, the etiology of the lung nodules frequently remains indeterminate and requires further evaluation. The approach to the management of indeterminate lung nodules ranges between observation with repeat chest CT scan, further diagnostic studies such as PET scan or invasive procedures to obtain tissue diagnosis. This article reviews the importance of the different radiological features of lung nodules. This is followed by an update on the approach to the management of the different types of small lung nodules.
Papers of special note have been highlighted as: ▪ of interest
References
- 1 Tuddenham WJ. Glossary of terms for thoracic radiology: recommendations of the Nomenclature Committee of the Fleischner Society. AJR Am. J. Roentgenol.143,509–517 (1984).Crossref, Medline, CAS, Google Scholar
- 2 Wahidi MM, Govert JA, Goudar RK et al. Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer? An ACCP evidence-based clinical practice guideline (2nd edition). Chest132,94S–107S (2007).▪ Includes the American College of Chest Physicians recommendations regarding the lung nodules management.Crossref, Medline, Google Scholar
- 3 Henschke CI, McCauley DI, Yankelevitz DF et al. Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet354,99–105 (1999).Crossref, Medline, CAS, Google Scholar
- 4 Ost D, Fein A. Evaluation and management of the solitary pulmonary nodule. Am. J. Respir. Crit. Care Med..162,782–787 (2000).Crossref, Medline, CAS, Google Scholar
- 5 Erasmus JJ, Connolly JE, McAdams HP et al. Solitary pulmonary nodules: part I. Morphologic evaluation for differentiation of benign and malignant lesions. Radiographics20,43–58 (2000).Crossref, Medline, CAS, Google Scholar
- 6 Tang AW, Moss HA, Robertson RJ. The solitary pulmonary nodule. Eur. J. Radiol.45,69–77 (2003).Crossref, Medline, CAS, Google Scholar
- 7 Ohwada A, Sato K, Tamori Y et al. Visible male nipple shadows in chest radiographs. Respirology10,111–115 (2005).Crossref, Medline, Google Scholar
- 8 Tan BB, Flaherty KR, Kazerooni EA et al. The solitary pulmonary nodule. Chest123(1 Suppl.),89S–96S (2003).Crossref, Medline, Google Scholar
- 9 Berrino F. Survival of cancer patients in Finland, 1955–1994. Acta Oncol.38,275–277 (1999).Crossref, Medline, CAS, Google Scholar
- 10 Suzuki K, Nagai K, Yoshida J et al. Prognostic factors in clinical stage I non-small cell lung cancer. Ann. Thorac. Surg.67,927–932 (1999).Crossref, Medline, CAS, Google Scholar
- 11 Rubins JB, Rubins HB. Temporal trends in the prevalence of malignancy in resected solitary pulmonary lesions. Chest109,100–103 (1996).Crossref, Medline, CAS, Google Scholar
- 12 Khouri NF, Meziane MA, Zerhouni EA et al. The solitary pulmonary nodule. Assessment, diagnosis, and management. Chest91,128–133 (1987).Crossref, Medline, CAS, Google Scholar
- 13 Ray JF 3rd, Lawton BR, Magnin GE et al. The coin lesion story: update 1976. Twenty years’ experience with thoracotomy for 179 suspected malignant coin lesions. Chest70,332–336 (1976).Crossref, Medline, Google Scholar
- 14 Higgins GA, Shields TW, Keehn RJ. The solitary pulmonary nodule. Ten-year follow-up of veterans administration-armed forces cooperative study. Arch. Surg.110,570–575 (1975).Crossref, Medline, CAS, Google Scholar
- 15 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.157,849–855 (1997).▪ Original study that provides predictors of malignancy in a solitary pulmonary nodule.Crossref, Medline, CAS, Google Scholar
- 16 American Cancer Society. Cancer Facts and Figures 2012 American Cancer Society, GA, USA (2012).Google Scholar
- 17 Winer-Muram HT. The solitary pulmonary nodule. Radiology239,34–49 (2006).Crossref, Medline, Google Scholar
- 18 Steele JD. The solitary pulmonary nodule. Report of a cooperative study of resected asymptomatic solitary pulmonary nodules in males. J. Thorac. Cardiovasc. Surg.46,21–39 (1963).Crossref, Medline, CAS, Google Scholar
- 19 Vance JW, Good CA, Hodgson CH et al. The solitary circumscribed pulmonary lesion due to bronchogenic carcinoma: a 3-year follow-up study of 94 surgically treated patients. Dis. Chest36,231–237 (1959).Crossref, Medline, CAS, Google Scholar
- 20 Gurney JW. Determining the likelihood of malignancy in solitary pulmonary nodules with Bayesian analysis. Part I. Theory. Radiology186,405–413 (1993).▪ Interesting study showing the value of the Bayesian analysis in predicting likelihood of malignancy in a solitary pulmonary nodule.Crossref, Medline, CAS, Google Scholar
- 21 Swensen SJ, Morin RL, Schueler BA et al. Solitary pulmonary nodule: CT evaluation of enhancement with iodinated contrast material – a preliminary report. Radiology182,343–347 (1992).Crossref, Medline, CAS, Google Scholar
- 22 Siegelman SS, Khouri NF, Leo FP, Fishman EK, Braverman RM, Zerhouni EA. Solitary pulmonary nodules: CT assessment. Radiology160,307–312 (1986).Crossref, Medline, CAS, Google Scholar
- 23 Sortini A, Carcoforo P, Ascanelli S et al. Significance of a single pulmonary nodule in patients with previous history of malignancy. Eur. J. Cardiothorac. Surg.20,1101–1105 (2001).Crossref, Medline, CAS, Google Scholar
- 24 Quint LE, Park CH, Iannettoni MD. Solitary pulmonary nodules in patients with extrapulmonary neoplasms. Radiology217,257–261 (2000).Crossref, Medline, CAS, Google Scholar
- 25 Parker MS, Leveno DM, Campbell TJ et al. AIDS-related bronchogenic carcinoma: fact or fiction? Chest113,154–161 (1998).Crossref, Medline, CAS, Google Scholar
- 26 Zerhouni EA, Stitik FP, Siegelman SS et al. CT of the pulmonary nodule: a cooperative study. Radiology160,319–327 (1986).Crossref, Medline, CAS, Google Scholar
- 27 Steele JD, Buell P. Asymptomatic solitary pulmonary nodules. Host survival, tumor size and growth rate. J. Thorac. Cardiovasc. Surg.65,140–151 (1973).Crossref, Medline, CAS, Google Scholar
- 28 Weiss W. Tumor doubling time and survival of men with bronchogenic carcinoma. Chest65,3–8 (1974).Crossref, Medline, CAS, Google Scholar
- 29 Garland LH, Coulson W, Wollin E. The rate of growth and apparent duration of untreated primary bronchial carcinoma. Cancer16,694–707 (1963).Crossref, Medline, CAS, Google Scholar
- 30 Nathan MH, Collins VP, Adams RA. Differentiation of benign and malignant pulmonary nodules by growth rate. Radiology79,221–232 (1962).Crossref, Medline, CAS, Google Scholar
- 31 Yankelevitz DF, Reeves AP, Kostis WJ et al. Small pulmonary nodules: volumetrically determined growth rates based on CT evaluation. Radiology217,251–256 (2000).▪ Demonstrates the accuracy of special CT scans in detecting small volumetric changes in the size of a pulmonary nodule, and correlation between these volumetric changes and the final diagnosis.Crossref, Medline, CAS, Google Scholar
- 32 Revel MP, Bissery A, Bienvenu M et al. Are two-dimensional measurements of small non-calcified pulmonary nodules reliable? Radiology231,453–458 (2004).Crossref, Medline, Google Scholar
- 33 Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am. J. Roentgenol.168,325–328 (1997).Crossref, Medline, CAS, Google Scholar
- 34 Zwirewich CV, Vedal S, Miller RR et al. Solitary pulmonary nodule: high-resolution CT and radiologic-pathologic correlation. Radiology179,469–476 (1991).Crossref, Medline, CAS, Google Scholar
- 35 Mahoney MC, Shipley RT, Corcoran HL et al. CT demonstration of calcification in carcinoma of the lung. AJR Am. J. Roentgenol.154,255–258 (1990).Crossref, Medline, CAS, Google Scholar
- 36 Seemann MD, Seemann O, Luboldt W et al. Differentiation of malignant from benign solitary pulmonary lesions using chest radiography, spiral CT and HRCT. Lung Cancer29,105–124 (2000).Crossref, Medline, CAS, Google Scholar
- 37 Furuya K, Murayama S, Soeda H et al. New classification of small pulmonary nodules by margin characteristics on high-resolution CT. Acta Radiol.40,496–504 (1999).Crossref, Medline, CAS, Google Scholar
- 38 Siegelman SS, Zerhouni EA, Leo FP et al. CT of the solitary pulmonary nodule. AJR Am. J. Roentgenol.135,1–13 (1980).Crossref, Medline, CAS, Google Scholar
- 39 Heitzman ER, Markarian B, Raasch BN et al. Pathways of tumor spread through the lung: radiologic correlations with anatomy and pathology. Radiology144,3–14 (1982).Crossref, Medline, CAS, Google Scholar
- 40 Bateson EM. An analysis of 155 solitary lung lesions illustrating the differential diagnosis of mixed tumours of the lung. Clin. Radiol.16,51–65 (1965).Crossref, Medline, CAS, Google Scholar
- 41 Stewart JG, MacMahon H, Vyborny CJ et al. Dystrophic calcification in carcinoma of the lung: demonstration by CT. AJR Am. J. Roentgenol.148,29–30 (1987).Crossref, Medline, CAS, Google Scholar
- 42 Grewal RG, Austin JH. CT demonstration of calcification in carcinoma of the lung. J. Comput. Assist. Tomogr.18,867–871 (1994).Crossref, Medline, CAS, Google Scholar
- 43 Swensen SJ, Brown LR, Colby TV et al. Pulmonary nodules: CT evaluation of enhancement with iodinated contrast material. Radiology194,393–398 (1995).Crossref, Medline, CAS, Google Scholar
- 44 Swensen SJ, Brown LR, Colby TV et al. Lung nodule enhancement at CT: prospective findings. Radiology201,447–455 (1996).Crossref, Medline, CAS, Google Scholar
- 45 Swensen SJ, Viggiano RW, Midthun DE et al. Lung nodule enhancement at CT: multicenter study. Radiology214,73–80 (2000).Crossref, Medline, CAS, Google Scholar
- 46 Jeong YJ, Lee KS, Jeong SY et al. Solitary pulmonary nodule: characterization with wash-in and washout features at dynamic multi-detector row CT. Radiology237,675–683 (2005).Crossref, Medline, Google Scholar
- 47 Yamashita K, Matsunobe S, Tsuda T et al. Solitary pulmonary nodule: preliminary study of evaluation with incremental dynamic CT. Radiology194,399–405 (1995).Crossref, Medline, CAS, Google Scholar
- 48 Yamashita K, Matsunobe S, Tsuda T et al. Intratumoral necrosis of lung carcinoma: a potential diagnostic pitfall in incremental dynamic computed tomography analysis of solitary pulmonary nodules? J. Thorac. Imaging12,181–187 (1997).Crossref, Medline, CAS, Google Scholar
- 49 Yoon HE, Fukuhara K, Michiura T et al. Pulmonary nodules 10 mm or less in diameter with ground-glass opacity component detected by high-resolution computed tomography have a high possibility of malignancy. Jpn. J. Thorac. Cardiovasc. Surg.53,22–28 (2005).Crossref, Medline, Google Scholar
- 50 Suzuki K, Asamura H, Kusumoto M et al. “Early” peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann. Thorac. Surg.74,1635–1639 (2002).Crossref, Medline, Google Scholar
- 51 Travis WD, Garg K, Kranklin WA et al. Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchoalveolar carcinoma. J. Clin. Oncol.23,3279–3287 (2005).Crossref, Medline, Google Scholar
- 52 Henschke CI, Yankelevitz DF, Mirtcheva R et al. CT screening for lung cancer: frequency and significance of part-solid and nonsolid nodules. AJR Am. J. Roentgenol.178,1053–1057 (2002).Crossref, Medline, Google Scholar
- 53 Lindell RM, Hartman TE, Swensen SJ et al. Five-year lung cancer screening experience: CT appearance, growth rate, location, and histologic features of 61 lung cancers. Radiology242,555–562 (2007).Crossref, Medline, Google Scholar
- 54 Takashima S, Sone S, Li F et al. Small solitary pulmonary nodules (< or = 1 cm) detected at population based CT screening for lung cancer: reliable high-resolution CT features of benign lesions. AJR Am. J. Roentgenol.180,955–964 (2003).Crossref, Medline, Google Scholar
- 55 Kui M, Templeton PA, White CS et al. Evaluation of the air bronchogram sign on CT in solitary pulmonary lesions. J. Comput. Assist. Tomogr.20,983–986 (1996).Crossref, Medline, CAS, Google Scholar
- 56 Kuriyama K, Tateishi R, Doi O et al. Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. AJR Am. J. Roentgenol.156,921–924 (1991).Crossref, Medline, CAS, Google Scholar
- 57 Woodring JH, Fried AM. Significance of wall thickness in solitary cavities of the lung: a follow-up study. AJR Am. J. Roentgenol.140,473–474 (1983).Crossref, Medline, CAS, Google Scholar
- 58 Woodring JH, Fried AM, Chuang VP. Solitary cavities of the lung: diagnostic implications of cavity wall thickness. AJR Am. J. Roentgenol.135,1269–1271 (1980).Crossref, Medline, CAS, Google Scholar
- 59 Muram TM, Aisen A. Fatty metastatic lesions in 2 patients with renal clear-cell carcinoma. J. Comput. Assist. Tomogr.27,869–870 (2003).Crossref, Medline, Google Scholar
- 60 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).Medline, CAS, Google Scholar
- 61 Christensen JA, Nathan MA, Mullan BP et al. Characterization of the solitary pulmonary nodule: 18F-FDG PET versus nodule-enhancement CT. AJR Am. J. Roentgenol.187,1361–1367 (2006).Crossref, Medline, Google Scholar
- 62 Lowe VJ, Fletcher JW, Gobar L et al. Prospective investigation of positron emission tomography in lung nodules. J. Clin. Oncol.16,1075–1084 (1998).▪ Important study showing the value of PET scans in the management of pulmonary nodules.Crossref, Medline, CAS, Google Scholar
- 63 Erasmus JJ, McAdams HP, Patz EF Jr. Non-small cell lung cancer: FDG-PET imaging. J. Thorac. Imaging14,247–256 (1999).Crossref, Medline, CAS, Google Scholar
- 64 Bryant AS, Cerfolio RJ, Klemm KM et al. Maximum standard uptake value of mediastinal lymph nodes on integrated FDG-PET–CT predicts pathology in patients with non-small cell lung cancer. Ann. Thorac. Surg.82,417–422 (2006).Crossref, Medline, Google Scholar
- 65 Schultz EM, Sanders GD, Trotter PR et al. Validation of two models to estimate the probability of malignancy in patients with solitary pulmonary nodules. Thorax63(4),335–341 (2008).Crossref, Medline, CAS, Google Scholar
- 66 Ost D, Fein AM, Feinsilver SH. Clinical practice. The solitary pulmonary nodule. N. Engl. J. Med.348,2535–2542 (2003).Crossref, Medline, Google Scholar
- 67 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. Radiology237,395–400 (2005).▪ Provides one of the most important and widely used guidelines for the management of lung nodules, mainly solitary nodules.Crossref, Medline, Google Scholar
- 68 Naidich DP, Bankier AA, Macmahon H et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology266(1),304–317 (2013).▪ Most updated guidelines in the management of lung nodules provide an important addition in the management of multiple lung nodules, as well as ground-glass nodules.Crossref, Medline, Google Scholar
- 69 Gould MK, Sanders GD, Barnett PG et al. Cost–effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann. Intern. Med.138,724–735 (2003).Crossref, Medline, Google Scholar
- 70 Shiner RJ, Rosenman J, Katz I et al. Bronchoscopic evaluation of peripheral lung tumors. Thorax43,887–889 (1988).Crossref, Medline, CAS, Google Scholar
- 71 Gasparini S, Ferretti M, Secchi EB et al. Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses. Experience with 1,027 consecutive cases. Chest108,131–137 (1995).Crossref, Medline, CAS, Google Scholar
- 72 Cortese DA, McDougall JC. Biopsy and brushing of peripheral lung cancer with fluoroscopic guidance. Chest75,141–145 (1979).Crossref, Medline, CAS, Google Scholar
- 73 Radke JR, Conway WA, Eyler WR et al. Diagnostic accuracy in peripheral lung lesions. Factors predicting success with flexible fiberoptic bronchoscopy. Chest76,176–179 (1979).Crossref, Medline, CAS, Google Scholar
- 74 Baaklini WA, Reinoso MA, Gorin AB et al. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest117,1049–1054 (2000).Crossref, Medline, CAS, Google Scholar
- 75 Gildea TR. Elctromagnetic navigation diagnostic bronchoscopy. Am. J. Respir. Crit. Care Med.174,982–989 (2006).Crossref, Medline, Google Scholar
- 76 Eberhardt R. Electromagnetic navigation diagnostic bronchoscopy in peripheral lung lesions. Chest131,1800–1805 (2007).Crossref, Medline, Google Scholar
- 77 Pearlstein DP, Quinn CC, Burtis CC, Ahn KW, Katch AJ. Electromagnetic navigation bronchoscopy performed by thoracic surgeons: one center’s early success. Ann. Thorac. Surg.93,944–949 (2012).Crossref, Medline, Google Scholar
- 78 Seijo LM, de Torres JP, Lozano MD et al. Diagnostic yield of electromagnetic navigation bronchoscopy is highly dependent on the presence of a bronchus sign on CT imaging: results from a prospective study. Chest138,1316–1321 (2010).Crossref, Medline, Google Scholar
- 79 Kurimoto N. Endobronchial ultrasonography for diagnosis of peripheral pulmonary lesions. Kyobu Geka60(8 Suppl.),724–733 (2007).Medline, Google Scholar
- 80 Steifort DP. Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis. Eur. Respir. J.37,902–910 (2011).Crossref, Medline, Google Scholar
- 81 Memoli JS, El-Bayoumi E, Pastis NJ et al. Using endobronchial ultrasound features to predict lymph node metastasis in patients with lung cancer. Chest140(6),1550–1556 (2011).Crossref, Medline, Google Scholar
- 82 Asano F, Matsuno Y, Matsushita T et al. Transbronchial diagnosis of a pulmonary peripheral small lesion using an ultrathin bronchoscope with virtual bronchoscopic navigation. J. Bronchol.9,108–111 (2000).Crossref, Google Scholar
- 83 Ishida T, Asano F, Yamazaki K et al.; Virtual Navigation in Japan Trial Group. Virtual bronchoscopic navigation combined with endobronchial ultrasound to diagnose small peripheral pulmonary lesions: a randomized trial. Thorax66,1072–1077 (2011).Crossref, Medline, Google Scholar
- 84 Lacasse Y, Wong E, Guyatt GH et al. Transthoracic needle aspiration biopsy for the diagnosis of localised pulmonary lesions: a meta-analysis. Thorax54,884–893 (1999).Crossref, Medline, CAS, Google Scholar
- 85 Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann. Intern. Med.155,137–144 (2011).Crossref, Medline, Google Scholar
- 86 Liao WY. US-guided Transthoracic cutting biopsy for peripheral thoracic lesions less than 3 cm in diameter. Radiology217,685–691 (2000).Crossref, Medline, CAS, Google Scholar
- 87 Yuan A. Ultrasound-guided aspiration biopsy of small peripheral nodules. Chest101,926–930 (1992).Crossref, Medline, CAS, Google Scholar
- 88 Jimenez MF. Prospective study on video-assisted thoracoscopic surgery in the resection of pulmonary nodules: 209 cases from the Spanish Video-Assisted Thoracic Surgery Study Group. Eur. J. Cardiothorac. Surg.19,562–565 (2001).Crossref, Medline, CAS, Google Scholar
- 89 Mack MJ, Hazelrigg SR, Landreneau RJ et al. Thoracoscopy for the diagnosis of the indeterminate solitary pulmonary nodule. Ann. Thorac. Surg.56,825–830 (1993).Crossref, Medline, CAS, Google Scholar
- 90 Park JS, Kim HK, Choi YS et al. Unplanned conversion to thoracotomy during video-assisted thoracic surgery lobectomy does not compromise the surgical outcome. World J. Surg.35,590–595 (2011).Crossref, Medline, Google Scholar
- 91 Suzuki K, Nagai K, Yoshida J et al. Video-assisted thoracoscopic surgery for indeterminate pulmonary nodules: indications for pre-operative marking. Chest115,563–568 (1999).Crossref, Medline, CAS, Google Scholar
- 92 Wang YZ, Boudreaux JP, Dowling A, Woltering EA. Percutaneous localization of pulmonary nodules prior to video-assisted thoracoscopic surgery using methylene blue and TC-99. Eur. J. Cardiothorac. Surg.37,237–238 (2010).Crossref, Medline, Google Scholar

