Approach to the solitary pulmonary Approach to the solitary pulmonary nodule A solitary pulmonary nodule

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    Approach to the solitary pulmonary nodule

    A solitary pulmonary nodule (SPN) is currently defined as a single pa- renchymal lung lesion which is 3 cm or less in diameter, and relatively spher- ical in contour. Some authorities consider that this definition does not ap- ply if there are major surrounding or associated abnormalities on a stan- dard chest radiograph. SPNs provide some of the more vexing clinical chal- lenges facing a pulmonary practitioner. These lesions are common, as ap- proximately 170,000 SPN are detected each year in the United States1. Approximately 1 in 500 standard chest radiographs in adults will show an SPN2 (GL).

    Solitary pulmonary nodules are malignant, usually bronchogenic car- cinomas, in 20-40% of cases3. Early resection of a malignant nodule im- proves the otherwise dismal prognosis of bronchogenic carcinoma2,3. In several reports, the 5-year survival has been as high as 75-80%4,5. Resec- tion of a benign nodule however, rarely confers significant benefit to the patient, and carries its own likelihoods for mortality and morbidity.


    The goals are to resect all malignant SPNs promptly, and, at the same time, to avoid resection of benign nodules where possible. The criterion has always been, and still is, that an indeterminate nodule should be regarded as malignant unless proof of benignity can be obtained. Conse- quently, the most important practical question is how to differentiate benign from malignant (or probably) SPNs prior to surgery.


    Two criteria for benignity of SPNs were proposed in the 1950s: nod- ular calcification and retrospective stability6 These are useful and still employed, although it is now clear that some modifications of this dic- tum are required7,8.

    Intranodular calcification may present a variety of appearances. Fea- tures indicative of benignity include central, diffuse, concentric rings or "popcorn" patterns. Patterns of eccentric calcification or multiple small

    L.T. Vaszar, G.A. Lillington

    Palo Alto Medical Foundation

    Key words: lung, nodule, diagnosis, lung cancer, screening

    Correspondence: Glen A. Lillington, M.D. Ombudsman Palo Alto Medical Foundation 795 El Camino Real Palo Alto, CA 94301

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    concentric deposits can be benign or malignant (Fig- ure 1), and in such cases, transthoracic needle biopsy or even diagnostic thoracotomy may still be indicated. Absence of calcification favors malignancy, but does not prove it. Even in a nodule with central calcifica- tion, malignancy is occasionally present9. With any ap- parently benign calcification pattern, it is prudent to monitor with serial x-rays or CT scans for several months or a year to detect growth, which might suggest malignancy.

    Retrospective stability implies little or no growth of the nodule, and is ordinarily assessed by comparison of any available prior chest x-rays with the current imag- es. Stability has traditionally been defined as no de- tectable increase in nodule size during the previous 24 months or longer. This criterion is not always absolute, mainly because attempting to detect and monitor growth of small nodules using standard x-rays some- times provides misleading results. In such instances, a small nodule may double or even triple in size before the increase in volume is recognized10. The accuracy of detecting growth is improved if the nodule is 1.0 cm or greater in diameter.

    Prior computed tomographic (CT) scans, if avail- able, are much more reliable in assessing retrospective stability than standard chest x-rays, particularly if the nodule is small (less than 10 mm in diameter). Retro-

    grade assessment of nodule growth by comparing CT images with standard chest x-ray images may lead to serious errors10.

    If the time interval between the first available and current images is less than 2 years, it is may be appro- priate in many instances to continue the evaluation with CT scans at 3-6 month intervals.


    Transthoracic needle aspiration biopsy. This rela- tively simple and safe test can be very valuable, and is often decisive. The test has a 80 to 95% sensitivity for malignancy, and a specificity of approximately 50%11. The biopsy needle is positioned under fluoroscopic or CT guidance.

    If the biopsy fails to establish that the nodule is ma- lignant, there are two further possibilities. The biopsy material may provide convincing evidence for a specif- ic benign lung disease, in which case the nodule is usu- ally classified as "benign". If the biopsy material is not definitive for either malignant or benign disease, the classification is "indeterminate". In the latter situation, it is often desirable to repeat the biopsy. On-site tech- nology for immediate sampling of the biopsy material facilitates repeat sampling in a single session and re- duces the likelihood of "indeterminate" results12,13.

    In the case of solitary nodules, an endobronchial biopsy through a bronchoscope has a relatively low sen- sitivity, unless the lesion is large in size and central in location. It is only employed occasionally in patients with SPNs.


    Computed Tomography (CT). Chest CT is not able to definitively establish malignancy or benignity in most solitary nodules, but it will often provide information that is very helpful in estimating the likelihood of ma- lignancy. CT is invaluable in determining whether the lesion is intrapulmonary, and provides much more ac- curate measurements of nodular diameters13. It may also demonstrate hitherto unsuspected multiple lesions in the lungs.

    CT may prove or strongly suggest that the lesion is

    Figure 1. Patterns of calcification in solitary pulmonary nod- ules. A, central; B, laminated; C, diffuse; D, popcorn; E, stip- pled, and F, eccentric. Patterns A through D are virtually al- ways indicative of benignity. Pattenrs E and F may occur in benign or malignant nodules. (From Lillington GA: Systemic diagnostic approach to pulmonary noduls, in AP Fishman [ed]: Pulmonary Disease and Disorders [ed 2]. New York, McGraw- Hill, 1988, p 1947. Used by permission).

  • 19PNEUMON Number 1, Vol. 16, January - April 2003

    benign if the nodule is a hamartoma, a vascular lesion, or has a benign calcification pattern not apparent in the standard chest x-rays.

    Features suggestive of malignancy include large size of the nodule, certain features of the nodule-lung in- terface (Figure 2), the absence of calcification, and de- monstrable proof of growth of the nodule with serial x- rays or CT scan studies. CT is superior to standard chest roentgenograms in all of these respects, and also pro- vides valuable information on the possible presence of enlarged mediastinal nodes.

    Magnetic Resonance Imaging (MRI) is not useful for the detection or identifying malignancy in solitary

    nodules, but it can be helpful in detecting and assessing hilar/and mediastinal adenopathy.

    Positron Emission Tomography (PET). The PET scan modality now plays a major role in the evaluation of solitary nodules14,15. The most accurate and helpful technique is a combined CT/PET scan, which is partic- ularly helpful for achieving precise localization of the abnormality. The overall sensitivity for tumors is 96.8%, but false negative results may occur with bronchoalve- olar tumors, and with malignant nodules less than 1 cm in diameter. As false positives may occur in active in- flammatory lesions, the specificity is only 77.8%14. A positive result strongly suggests malignancy and sur- gery should be actively considered. A negative PET scan strongly suggests benignity, but does not absolutely rule out malignancy.

    PET scans are also very helpful in detection of hi- lar, mediastinal and even distant metastases16.


    An estimate of the probability that the solitary nod- ule is a cancer is useful in the formulation of manage- ment strategies. The value of PCA can be calculated by an assessment of "predictor variables", which include clinical data (age, smoking history, presence or absence of previous malignancies) and radiographic character- istics (position of nodule in the lung, diameter of the nodule, edge characteristics, cavity wall thickness, and presence or absence of calcifications). Bayesian analy- sis17,18 or logistic regression19 can be employed to pro- vide a quantitative estimation (PCA) that the SPN is malignant.

    Calculating the PCA of SPNs is simplified by on- line algorithms, which can be accessed from the Inter- net with the following URL: SPN/SPNProb.html. Experienced observers are capa- ble of estimating PCA with considerable accuracy in many cases by reviewing the predictor variables with- out formal calculations of probability.


    In practice, most SPNs initially fall into the catego-

    Figure 2. Characteristic appearances of nodule edges. Type I is sharp and smooth and the probability of cancer based on this is 20%. Type 2 is sharp but lobulated, and the probability that the nodule is malignant is about 45%. Type 3 shows irregular undulations, and one or two spiculations. The likelihood of ma- lignancy is 2:1 in this case. Type 4. There are multiple spicula- tions. This has been termed "corona radiata" or "corona mali- gna". The odds favoring malignancy are 14:1 in such cases. (Re- draw from Siegelman SS, Khouri NF, Fishman EK, et al: Sol- itary pulmonary nodules: CT assessment. Radiology 1986; 160(8): 307-312, Used by permission).

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