Solitary Pulmonary Nodules: Detection, Characterization, and

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  • AJR:188, January 2007 57

    AJR 2007; 188:5768


    American Roentgen Ray Society 11/30/06

    Jeong et al.Solitary Pulmonary Nodules

    C h e s t I m ag i n g Pe r s p e c t i ve

    Solitary Pulmonary Nodules: Detection, Characterization, and Guidance for Further Diagnostic Workup and Treatment

    Yeong Joo Jeong1,2

    Chin A. Yi1

    Kyung Soo Lee1

    Jeong YJ, Yi CA, Lee KS

    Keywords: chest imaging, dynamic CT, lung, lung neoplasms, PET/CT, screening, solitary pulmonary nodules


    Received December 13, 2005; accepted after revision May 25, 2006.

    1Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea. Address correspondence to K. S. Lee (

    2Present address: Department of Diagnostic Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan, Korea.

    CMEThis article is available for CME credit. See for more information.

    OBJECTIVE. The purpose of our study is to improve radiologists understanding of theclinical issues involved in making a diagnosis and to guide further diagnostic workup and treat-ment of solitary pulmonary nodules (SPNs).

    CONCLUSION. Information on the morphologic and hemodynamic characteristics ofSPNs provided by dynamic helical CT, with high specificity and reasonably high accuracy, canbe used for initial assessment. PET/CT is more sensitive at detecting malignancy than dynamichelical CT, and all malignant nodules may be potentially diagnosed as malignant by both tech-niques. Therefore, PET/CT may be selectively performed to characterize SPNs that show in-determinate results at dynamic helical CT.

    T screening has increased the de-tection rate of small pulmonarynodules (SPNs). The tissue charac-terization of subcentimeter nod-

    ules, still a challenge to radiologists, can beperformed using serial volume measurementsfrom CT. Video-assisted thoracoscopic surgeryremoval after nodule localization may be per-formed for the diagnosis and treatment of asubcentimeter nodule. In this perspective, wepropose how to improve our understanding ofthe clinical issues involved in making a diag-nosis and to guide further diagnostic workupand treatment of SPNs.

    SPNs are defined as focal, round, or oval ar-eas of increased opacity in the lung with diam-eters of 3 cm [1]. The characterization ofSPNs is a major concern not only to radiolo-gists but also to clinicians because malignantlesions account for only 6080% of resectedpulmonary nodules [24]. The goal of the ra-diologic evaluation of SPNs is to noninvasivelydifferentiate benign from malignant lesions asaccurately as possible. Morphologic evalua-tions can help differentiate benign and malig-nant nodules when they have typical benign ormalignant features, but there is considerableoverlap between benign and malignant nodulesin terms of their morphologic presentations [5].

    Various strategies other than morphologicevaluations have been applied to the differen-tiation of malignant and benign nodules,which include growth rate assessment [6],Bayesian analysis [7], and hemodynamic

    characteristics on dynamic helical CT [810].In addition, the assessment of nodular meta-bolic characteristics on 18F-FDG PET [11]and pathologic evaluations using transtho-racic needle aspiration, transthoracic needlebiopsy, or video-assisted thoracoscopic sur-gery have also been used for characterizingSPNs. However, no single diagnostic algo-rithm can be applied to all cases.

    The aim of this perspective is to improve ourunderstanding of the clinical issues involved inmaking a diagnosis and to guide further diag-nostic workup and treatment of SPNs.

    DetectionAlthough new diagnostic techniques have

    been introduced, the detection of lung nod-ules on imaging is difficult. CT screening hasincreased the detection rate of small nodularattenuations, including those of early periph-eral lung cancer [1214]. Despite the higherspatial and contrast resolutions of CT, nodu-lar lesions are missed on chest CT. Missed le-sions occur because of failures of detection.In a study by Ko et al. [15], a small nodulesize of 5 mm in diameter (nodule detectionsensitivity: 5 mm vs > 5 mm, 74% vs 82%),ground-glass opacity nodules (nodule detec-tion sensitivity: ground-glass opacity vssolid, 65% vs 83%), and lesion location (nod-ule detection sensitivity: central vs periph-eral, 61% vs 80%) were shown to be majorfactors that contribute to the difficulty in de-tecting nodules. Nodule detection can be im-


  • Jeong et al.

    58 AJR:188, January 2007 11/30/06

    Fig. 1Screen shot of computer-aided detection system in 44-year-old woman shows 7-mm nodule in right apex (arrow) adjacent to mediastinal great vessels that was not detected on computer-assisted detection system but was detected by radiologists.

    proved by advances in computer-aided detec-tion (CAD) systems that are being developedand evaluated to provide a second perspec-tive for nodule detection on CT. The use ofCAD can help improve radiologist perfor-mance for the detection of unidentified lungcancers during lung cancer screening withCT [16, 17]. However, Lee et al. [18] showedthat the sensitivity of a CAD system (81%)did not significantly differ from that of radi-ologists (85%). Radiologists were more sen-sitive at detecting nodules attached to otherstructures (Fig. 1), whereas CAD was betterat detecting isolated nodules and those thatwere 5 mm in diameter [18].

    Morphologic EvaluationEvaluation of the specific morphologic

    features of SPNs can help differentiate benignfrom malignant nodules. Small, smooth nod-ules with well-defined margins are suggestiveof, but not diagnostic for, benignity; and alobulated contour or an irregular or spiculatedmargin with distortion of adjacent vessels istypically associated with malignancy [5]. Dif-fuse, laminated, central nodular, and pop-cornlike calcifications within nodules suggestbenignity. On the other hand, eccentric orstippled calcifications have been described inmalignant nodules. Fat or calcification maybe observed in up to 50% of pulmonary

    A B C

    Fig. 2Volume measurement of pulmonary nodule in 47-year-old man with lung adenocarcinoma on computer-aided detection system.A, Application of region of interest to nodule automatically leads to volume measurement with outline delineation and nodule segmentation.B, Volume imaging of nodule and resultant volume of 99 mm3 are shown.C, Volume imaging shows 127 mm3 of nodule at follow-up after 93 days. Calculated volume doubling time is 145 days.

    hamartoma [19]. In a study by Jeong et al.[10], multivariate analysis was used to iden-tify criteria independently associated with adiagnosis of a malignant nodule that had ahigher odds ratio for malignancy than otherradiologic finding criteria; the criteria were alobulated margin, a spiculated margin, andthe absence of a satellite nodule. Consider-able overlap exists between the internal char-acteristics (air bronchogram, cavitation, wallthickness, attenuation, and so forth) of benignand malignant nodules. Initial morphologicevaluations of SPNs often result in nonspe-cific findings and further evaluations to ex-clude malignancy.

    When interpreting screening CT images, ra-diologists must search for lung nodules, differ-entiate malignant lesions from benign nodules,and finally, recommend follow-up actions forthese detected lesions. The results of the EarlyLung Cancer Action Project (ELCAP) [13]suggested that nodules with pure (nonsolid) ormixed (partially solid) ground-glass opacity onthin-section CT are more likely to be malig-nant than are those with solid opacity. Li et al.[20] more specifically evaluated the character-istic thin-section CT findings of malignant andbenign nodules detected on screening CT.Among nodules with pure ground-glass opac-ity, a round shape was found more frequentlyfor malignant lesions (65%) than for benign le-sions (17%); mixed ground-glass opacity, asubtype that has ground-glass opacity in theperiphery and a high-attenuation zone in thecenter, was seen much more often in malignant

  • Solitary Pulmonary Nodules

    AJR:188, January 2007 59 11/30/06

    lesions (41%) than in benign lesions (7%).Among solid nodules, a polygonal shape or asmooth margin was present less frequently inmalignant than in benign lesions.

    Growth Rate AssessmentDetermination of growth rate by comparing

    sizes on current and prior images is an impor-tant and cost-effective step in the evaluation ofSPNs. The absence of detectable growth over a2-year period of observation is a reliable crite-rion for establishing that a pulmonary nodule isbenign [21]. Despite widespread acceptance,the value of 2-year stability for the diagnosis ofa benign nodule may not be sufficient forground-glass opacities and suspected bronchi-oloalveolar carcinoma [22]. In addition, it isdifficult to reliably detect growth in small (< 1cm) nodules. To overcome this limitation, ithas been proposed that the growth rate of smallnodules be assessed using serial volume mea-surements rather than diameter [23]. Computersoftware programs that automatically enable anodule volume calculation have becomewidely available. Moreover, computer-aided3D quantitative volume measurement methodshave been developed and applied clinically[2325] (Fig. 2).

    However, all these volumetric methods arefocused on solid pulmonary nodules. Few re-ports have dealt with nodule volumetric meth-ods for ground-glass opacity nodules [26]. Vol-umetry for ground-glass opacity or semisolid (asolid nodule containing a ground-glass opacitycomponent) nodules is more d