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THE SOLITARY PULMONARYNODULE
Johnsey L. Leef III, MD, and Jeffrey S. Klein, MD
The evaluation of a solitary pulmonarynodule (SPN) is a common diagnostic di-lemma that has become more prevalent withthe increasing use of helical CT.21 The ultimategoal of imaging in the evaluation of SPNs isto accurately distinguish benign from poten-tially malignant lesions. This has practical im-portance because the ultimate goal of imagingis to avoid referring a patient with a benignSPN for unnecessary surgical resection, whilebeing certain not to characterize a small ma-lignant SPN incorrectly that may representresectable (i.e., curable) early stage lung can-cer as benign.
Although most SPNs prove to be benign,the distinction of benign from malignant le-sions can be difficult. One of the most im-portant but understated aspects of SPN evalu-ation is to be certain that a focal opacitydetected radiographically actually representsa solitary intrapulmonary lung nodule. Oncethis has been determined, demographic fea-tures including patient age, smoking history,history of prior malignancy, and environmen-tal exposures are important in guiding evalu-ation because these factors influence the post-test probability of malignancy independent ofimaging characteristics of the lesion in ques-tion. An important characteristic of the lesionthat can often be discerned from a review ofprior radiographs is an assessment of growthrate that helps determine the likelihood of
From the Department of Radiology, Fletcher Allen Health Care, and University of Vermont College of Medicine,Burlington, Vermont
RADIOLOGIC CLINICS OF NORTH AMERICA
VOLUME 40 NUMBER 1 JANUARY 2002 123
malignancy. Following this preliminary as-sessment, assuming the risk of malignancyremains significant, most patients undergothin-section CT for detailed analysis of size,internal density, and morphologic features ofthe SPN.28 Adhering to strict criteria for de-fining benign SPNs leaves most lesions inde-terminate. These patients require more detailednodule evaluation with contrast-enhanced CTor positron emission tomography (PET); someultimately require biopsy or resection for de-finitive diagnosis.
An SPN is defined as a single round intra-parenchymal opacity, at least moderatelywell-marginated and no greater than 3 cmin maximum diameter. This size limitation isbased on the fact that most solitary lung le-sions larger than 3 cm in diameter (termedmasses) are malignant, whereas most lesionsless than 3 cm are benign. In addition, thedetection of benign patterns of calcification ina solitary lung lesion allows the confidentdiagnosis of a benign lesion only when it isless than 3 cm.12
It is important when considering a radio-graphically detected SPN to be certain thatthe density in question is truly solitary, lieswithin the lung, and represents a nodule. As
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many as 50% of patients with suspected SPNsdetected radiographically actually prove tohave multiple nodules on CT evaluation.6This is particularly important because thepresence of multiple lung nodules is sugges-tive of metastatic or granulomatous diseaseand requires a different approach than theSPN. Even when an SPN is detected as anincidental finding on helical CT or in thecourse of screening for lung cancer, a detailedanalysis of both lungs, particularly with thin-section collimation (i.e., 5 mm) and over-lapping reconstructions viewed on a worksta-tion, can allow detection of multiple lesionsthat may alter the diagnostic evaluation.25
The intrapulmonary localization of a nodu-lar opacity seen on only a single radiographicprojection can likewise be difficult. For a le-sion to be considered intrapulmonary on con-ventional radiographs it must be a discreteopacity completely circumscribed by aeratedlung on orthogonal projections. Pseudonod-ules caused by EKG pads or other devices onthe patients skin surface can mimic intrapul-monary lesions on frontal radiographs. Cuta-neous lesions including moles, nipple shad-ows, hemangiomas, neurofibromas, andlipomas that protrude from the patients skinand are surrounded by atmospheric air alsomay appear intrapulmonary on a single ra-diographic projection (Fig. 1). Careful exami-nation of the skin surface usually readilyidentifies these lesions; if necessary these can
Figure 1. Skin lesion mimicking intrapulmonary nodule. A, Frontal chest radiograph demonstrates avague nodular opacity overlying the right midlung. B, Lateral radiograph shows that the densityrepresents a cutaneous lesion projecting from the posterior chest wall. Physical examination con-firmed the presence of a cutaneous hemangioma.
be confirmed easily by repeat frontal andoblique radiographs or limited chest fluoros-copy following placement of localizing metal-lic markers. Other lesions that may mimic aSPN include sclerotic bone lesions, such asbone islands; healing rib fractures; and spinalosteophytes. Although these usually are eas-ily recognized after review of prior radio-graphs, detailed views of the area in question,chest fluoroscopy, or CT may be necessaryin selected cases. Likewise, mediastinal andpleural lesions that are pedunculated andproject into the lung (i.e., pleural plaques)can appear as SPNs when viewed en face. Atangential view of the region of contact be-tween the lesion and the mediastinum orpleura, however, usually shows an indistinctborder that forms obtuse angles.
Many apparent focal nodular opacities seenradiographically actually represent vascularstructures that are tortuous, seen en face, orare superimposed on other vascular struc-tures that lie in the same sagittal plane. Theseusually can be identified by review of priorradiographs taken at slightly different obliq-uities or by performing chest fluoroscopy; CTshould be reserved for equivocal cases. Occa-sionally, a mucocele within a dilated bron-chus appears as a SPN. This diagnosis is usu-ally readily apparent by detailed review ofthin-section CT images that show a tubularor branching lesion of water attenuation; re-sidual air between the mucocele and bron-
THE SOLITARY PULMONARY NODULE 125
chial wall is seen sometimes. Other presumedSPNs are found to represent linear parenchy-mal scars seen en face. Unless this is easilyrecognized on current or prior radiographicstudies, thin-section CT is often necessary todisplay the two-dimensional linear nature ofthe opacity and help distinguish this lesionfrom a spherical nodule.
The differential diagnosis of a SPN is exten-sive and includes neoplastic, infectious, in-flammatory, vascular, traumatic, and congeni-tal conditions (Table 1). Most benign SPNs aregranulomas, hamartomas, or intrapulmonarylymph nodes, whereas bronchogenic carcino-mas represent most malignant SPNs.
Once a SPN has been definitively identi-fied, a detailed investigation almost invari-ably ensues. Specific clinical features affectthe likelihood of benignancy or malignancy,however, and in conjunction with the imagingcharacteristics of the lesion can impact boththe diagnostic approach and choice of thera-peutic options. Bayesian analysis allows for a
Table 1. DIFFERENTIAL DIAGNOSIS OF A SOLITARY PULMONARY NODULE
Neoplasm Benign HamartomaInflammatory pseudotumor
Malignant Bronchogenic carcinomaCarcinoid tumorLymphoma (Non-Hodgkins)Metastasis
Infection Granuloma MycobacteriaFungi
Septic embolusAbscess Bacteria (anaerobes, Staphylococcus,
Round pneumonia PneumococcusParasitic Echinococcus
Dirofilaria (dog heartworm)Inflammatory Connective tissue Wegeners granulomatosis
Rheumatoid (necrobiotic) noduleSarcoidosis (rare)
Vascular Arteriovenous malformationHematomaPulmonary infarctPulmonary artery aneurysmPulmonary venous varix
Airway Congenital lesion Bronchogenic cystBronchial atresia
more precise determination of the likelihoodof malignancy by combining radiographicfindings with clinical information (specificallyage, smoking history, and symptoms) to cal-culate mathematically the probability of ma-lignancy of a specific SPN. Bayes theoremuses an odds-ratio formula where the oddsof malignancy are divided by the odds ofmalignancy plus one. The equation for de-termining the overall odds of malignancy iscalculated by multiplying the patients priorodds of malignancy by the radiographic like-lihood ratio of malignancy by the clinical like-lihood ratio of malignancy. In this equation,the prior odds of malignancy are the preva-lence of malignancy for a given populationdivided by the prevalence of benign diseaseof that population.14 The likelihood of malig-nancy ratios are intuitive measures of diag-nostic information provided by radiographictest results or clinical findings.1, 14 Clinical in-formation or radiographic test results strong-ly suggestive of malignancy have a likelihoodratio much greater than one, whereas thosefindings suggestive of benignity have a likeli-hood ratio close to zero, and information ortest results that are considered to contain nodiagnostic information have a likelihood ratioof one.14
The clinical factors to consider in evalu-ating the likelihood of malignancy include
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patient age; smoking history; symptoms;comorbid conditions (particularly severe em-physema); history and type of prior malig-nancy; and environmental exposures. For ex-ample, a 30-year-old nonsmoking patientwithout a history of malignancy found tohave a smooth round SPN has a high likeli-hood of a benign lesion and radiologic followupto ensure stability is a reasonable and cost-effective approach. Conversely, one could ar-gue that a spiculated SPN in a 50-year-oldcigarette smoker should proceed to immedi