Heber MacMahon, MB,BCh, BAO

John H. M. Austin, MDGordon Gamsu, MDChristian J. Herold, MDJames R. Jett, MDDavid P. Naidich, MDEdward F. Patz, Jr, MDStephen J. Swensen, MD

Published online10.1148/radiol.2372041887

Radiology 2005; 237:395–400

1 From the Department of Radiology,University of Chicago, 5841 S Mary-land Ave, MC2026, Chicago, IL 60637(H.M.); Department of Radiology, Co-lumbia University Medical Center,New York, NY (J.H.M.A.); Departmentof Radiology, New York Hospital, Cor-nell Medical Center, New York, NY(G.G.); Department of Radiology, Uni-versity of Vienna Medical School, Vi-enna, Austria (C.J.H.); Departments ofMedicine (J.R.J.) and Diagnostic Radi-ology (S.J.S.), Mayo Clinic College ofMedicine, Rochester, Minn; Depart-ment of Radiology, NYU Medical Cen-ter, New York, NY (D.P.N.); and De-partment of Radiology, Duke Univer-sity Medical Center, Durham, NC(E.F.P.). Received November 5, 2004;revision requested January 5, 2005; re-vision received March 3; accepted May2. Address correspondence to H.M.(e-mail: macm@midway.uchicago.edu).© RSNA, 2005

Guidelines for Management ofSmall Pulmonary NodulesDetected on CT Scans:A Statement from theFleischner Society1

Lung nodules are detected very commonly on computed tomographic (CT) scans ofthe chest, and the ability to detect very small nodules improves with each newgeneration of CT scanner. In reported studies, up to 51% of smokers aged 50 yearsor older have pulmonary nodules on CT scans. However, the existing guidelines forfollow-up and management of noncalcified nodules detected on nonscreening CTscans were developed before widespread use of multi–detector row CT and stillindicate that every indeterminate nodule should be followed with serial CT for aminimum of 2 years. This policy, which requires large numbers of studies to beperformed at considerable expense and with substantial radiation exposure for theaffected population, has not proved to be beneficial or cost-effective. During thepast 5 years, new information regarding prevalence, biologic characteristics, andgrowth rates of small lung cancers has become available; thus, the authors believethat the time-honored requirement to follow every small indeterminate nodule withserial CT should be revised. In this statement, which has been approved by theFleischner Society, the pertinent data are reviewed, the authors’ conclusions aresummarized, and new guidelines are proposed for follow-up and management ofsmall pulmonary nodules detected on CT scans.© RSNA, 2005

Until now, it has been the accepted standard of practice to regard all noncalcified pulmo-nary nodules as potentially malignant lesions that require close monitoring until provedstable over a period of 2 years (1,2). This approach was adopted prior to the widespread useof computed tomography (CT) and was based on the observation that a substantialproportion of noncalcified nodules that were detected at chest radiography turned out tobe lung cancers. These nodules were almost all larger than 5 mm in diameter, and mostwere in the 1–3-cm range.

Since the introduction of helical CT in the early 1990s and multi–detector row CT in thelate 1990s, the detection of focal rounded pulmonary opacities (“nodules”) as small as 1–2mm in diameter has become routine. In fact, the majority of smokers who undergothin-section CT have been found to have small lung nodules, most of which are smallerthan 7 mm in diameter (3). However, the clinical importance of these extremely smallnodules differs substantially from that of larger nodules detected on chest radiographs, inthat the vast majority are benign. This issue has been highlighted in several recentpublications on CT screening for lung cancer, and the positive relationship of lesion sizeto likelihood of malignancy has been clearly demonstrated (4,5).

The only current guidelines in the radiology literature for management of small nodulesare those that have been developed in the context of lung cancer screening programs(6–8). However, subjects who undergo lung cancer screening in most countries areselected on the basis of age, substantial smoking history, absence of serious comorbiddisease, and willingness to participate in all necessary follow-up imaging and intervention.Also, these programs tend to take an aggressive approach to follow-up and early interven-

Editorials

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tion, with a view to achieving the highestpossible cure rate while gaining furtherinsight into the behavior and character-istics of small malignant lesions. There-fore, patients whose nodules are detectedincidentally during the course of CT per-formed for other reasons should not nec-essarily be treated in the same way assubjects in a screening program. Nonethe-less, although CT screening has not as yetbeen proved to help reduce mortality fromlung cancer, these programs provide animportant source of information for deter-mining the optimal management of “inci-dental” nodules detected in other situa-tions.

Our intent in this position statement isto provide practical guidelines for themanagement of small pulmonary nod-ules that are detected during the courseof CT examinations performed for pur-poses other than lung cancer screening.We recognize that this issue is complexand difficult to reduce to a simple algo-rithm. We also realize that the definitionof a pulmonary nodule is itself elusive,and that not all focal opacities qualify asnodules. Yet, we believe that there is apractical need in the medical communityfor guidance in this area.

BACKGROUND

Available data indicate that fewer than1% of very small (�5-mm) nodules inpatients without a history of cancer willdemonstrate malignant behavior (ie, de-tectable growth or metastases over a pe-riod of 2 or more years) (5,7,9). Nonethe-less, multiple follow-up examinationsover a 2-year period are commonly per-formed when such nodules are detectedincidentally. Guidelines for the manage-ment of the solitary pulmonary nodulewere published in 2003 by the AmericanCollege of Chest Physicians (2) and in areview in by Ost and colleagues in theNew England Journal of Medicine (1). How-ever, neither of these articles specificallyaddressed the issue of the very small nod-ule that is detected as an incidental find-ing on a CT scan. Ost and colleagues con-cluded by recommending CT follow-upat 3, 6, 12, 18, and 24 months for all“low-probability” indeterminate nodules(ie, nodules with a low likelihood of be-ing cancer), regardless of size (1). TheAmerican College of Chest Physiciansrecommendation for management of in-determinate solitary nodules was similar,with the proposal for 3-, 6-, 12-, and 24-month CT follow-up intervals, also with-out any specified lower size limit for a

nodule that would qualify for this proto-col (2).

The rationale for recommending serialfollow-up studies for all indeterminatesmall nodules is that some of them willturn out to be cancers and that early in-tervention will provide an opportunityfor cure. The “downside” of this policyincludes potential morbidity and mor-tality from surgery for benign nodulesand other false-positive findings, poorutilization of limited resources, in-creased health care costs, unnecessarypatient anxiety, loss of credibility forradiologists who may seem to recom-mend excessive numbers of CT scanswith little benefit, and increased radia-tion burden for the affected popula-tion. The radiation issue is particularlyimportant in younger patients andmust be taken into account in deter-mining appropriate follow-up strategies(10–13).

There remains a growing need to reex-amine the radiologic approach to smallnodules, particularly when CT is per-formed for indications other than screen-ing. Several fundamental issues need tobe considered before an imaging strategyis recommended. Since the decision toperform follow-up studies relies on size,lesion characteristics (eg, morphology),and growth rates (typically described asdoubling time), an understanding ofthese features and their relationship tomalignancy should dictate further evalu-ation. In addition, the patient’s risk pro-file, including age and smoking history,needs to be integrated into the diagnosticalgorithm.

Nodules Detected on CT Scans

During the past 5 years, new informa-tion regarding the morphology, biologiccharacteristics, and growth rates of smalllung cancers has become available fromCT lung cancer screening programsthroughout the world. Selected studiesare summarized below as representativeof the present state of knowledge in thisarea.

Henschke et al (9) published the initialresults from the Early Lung Cancer Ac-tion Project CT screening project in 1999.They enrolled 1000 asymptomatic smok-ers or ex-smokers with at least 10 pack-years of cigarette smoking who were aged60 years or older. Screening CT studieswere performed with 10-mm collima-tion. The investigators found noncalci-fied nodules in 23% of subjects and ma-lignant nodules in 2.7%. All detectednodules were subjected to thin-section

CT. If the nodule did not exhibit un-equivocally benign characteristics (be-nign pattern of calcification, smoothmargins, and size less than 20 mm), itwas followed up with thin-section CT at3 months and subsequently at 6, 12, and24 months in the absence of change.Only one cancer was less than 5 mm indiameter at the time of detection in thebaseline (10-mm-collimation) study. Theresults of the repeat screening were re-ported in 2001. Seven new cancers weredetected at the repeat screening; three ofthese were 5 mm in size (defined as theaverage of the length and width in thatstudy); all the other proved cancers werelarger (8).

Swensen et al (7) reported the results ofthe Mayo Clinic Lung Cancer ScreeningTrial after completion of three annuallow-dose CT examinations in 1520 smok-ers. The subjects were aged 50 years orolder and had a smoking history of 20pack-years or more. Two years after base-line screening, 2832 noncalcified pulmo-nary nodules had been identified in 1049(69%) participants. Thirty-six lung can-cers were diagnosed with the aid of CT(2.6% of participants, 1.4% of nodules):26 at baseline (prevalence) and 10 at sub-sequent annual (incidence) CT examina-tions. Thirty-two (80%) of these cancerswere larger than 8 mm, and only one wassmaller than 5 mm at the time of detec-tion. Two cancers were detected by usingsputum cytology, and there were two in-terval cancers.

Benjamin et al (14) reported the resultsof a retrospective review of 334 non-screening cases in which a lung nodule ornodules were detected that were less than10 mm in their long axis and for whichfollow-up CT was recommended. Thesenodules were identified from 3446 con-secutive chest CT studies performed attheir institution. Among patients with anodule, 87 patients had “definitive” fol-low-up results (2 years without change orbiopsy). Nodules in 10 (11%) of thesepatients were malignant. Nine of thesecases were metastases from known pri-mary tumors, and one turned out to be ametastasis from an occult primary tumor.This high incidence of metastases is areflection of the patient population thatwas used for this study, in that 56% ofthe included patients had a known pri-mary tumor. The authors of that articlesuggested that the malignancy rate insmall nodules in patients without aknown neoplasm may be as low as 1%and that follow-up may not be necessaryin such cases.

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Nodule Size

On the basis of analysis of informationfrom the ongoing Mayo Clinic CTScreening Trial, Midthun et al (4) re-ported that fewer than 1% of very small(�5-mm) nodules in patients without ahistory of cancer were malignant. Theyindicated a likelihood of malignancy of0.2% for nodules smaller than 3 mm,0.9% for those 4–7 mm, 18% for those8–20 mm, and 50% for those larger than20 mm.

Henschke and colleagues (5) recentlyaddressed the issue of optimal follow-upintervals for nodules smaller than 5 mmin diameter. They performed a retrospec-tive review of a total of 2897 baselinescreening studies performed between1993 and 2002 in order to identify thosesubjects with noncalcified nodules that,at initial detection, were (a) smaller than5 mm in diameter and (b) 5–9 mm indiameter. In accordance with the screen-ing program guidelines, indeterminatenodules were rescanned at 3-, 6-, and 12-month intervals, while some in the5–9-mm range that had particularly sus-picious morphology were recommendedfor biopsy. On the basis of the results ofthese follow-up studies and biopsies, theauthors determined that when the largestnoncalcified nodule was smaller than 5mm in diameter (378 patients), a fol-low-up study in 12 months would haveresulted in no case of delayed diagnosis,compared with more aggressive short-term follow-up. However, when the larg-est nodule was 5–9 mm in diameter, ap-proximately 6% of cases (all of whichwere malignant) showed interval nodulegrowth detectable on 4–8-month fol-low-up scans. Therefore, they recom-mended that patients with nodules nolarger than 5 mm in diameter on a base-line screening CT scan should be referredfor repeat annual screening in 12 monthstime, with no interval scans. This recom-mendation differs only slightly from thecurrent protocol for the ongoing Na-tional Lung Screening Trial, in which pa-tients with nodules smaller than 4 mm indiameter are recommended to return forscreening after 12 months, without inter-val scans or other work-up. Note thatthese recommendations refer to high-risksubjects who have enrolled in a screeningprogram.

A further practical issue arises in thefollow-up to detect interval growth ofvery small nodules. Comparison of cur-rent and previous scans can be performedby using hard copy with manual mea-surement, soft copy with electronic cali-

pers, or software that performs auto-mated volumetric measurement of thenodule (15). The minified display usedfor hard copy makes accurate measure-ment of subcentimeter nodules virtuallyimpossible. Even with a state-of-the-artsoft-copy display and electronic calipers,substantial inter- and intrareader varia-tions in two-dimensional measurementshave been documented (16). Revel andcolleagues (16) determined that two-di-mensional measurements obtained withelectronic calipers were unreliable as abasis for distinguishing benign from ma-lignant solid nodules in the 5–15-mmsize range. Limited studies (15,17) thathave been performed with automatedthree-dimensional analysis suggest thatsuch systems can be considerably moreaccurate and consistent than unaidedradiologists in determining intervalchanges in small nodules. However, Kos-tis and colleagues (18) have shown thateven sophisticated automated volume-measurement methods are susceptible toerrors due to motion artifacts or segmen-tation problems, particularly in the caseof very small nodules.

Growth Rate

Hasegawa et al (19) reported an analy-sis of the growth rates of small lung can-cers detected during a 3-year mass screen-ing program. They classified nodules asground-glass opacity, as ground-glassopacity with a solid component, or assolid. Mean volume doubling times were813 days, 457 days, and 149 days, respec-tively, for these three types, all of whichwere significantly different. In addition,the mean volume doubling time for can-cerous nodules in nonsmokers was signif-icantly longer than that for cancerousnodules in smokers. The mean volumedoubling time was also significantlylonger for nodules not visible on chestradiographs (presumably a function oftheir smaller average size and/or theirlesser average opacity). These data furthersupport the use of extended follow-upintervals for small nonsolid or partlysolid nodules, even in high-risk patients.Authors of a number of other series(20,21) have confirmed similar findingsand have estimated the median tumordoubling times, assuming a constantgrowth rate to be in the 160–180-dayrange. Authors of all of these reports,however, recognize wide variations, andin one study 22% of tumors had a vol-ume doubling time of 465 days or more(21). Note that a 5-mm nodule with adoubling time of 60 days will reach a

diameter of 20.3 mm in 12 months,whereas a similar nodule with a doublingtime of 240 days would reach a diameterof only 7.1 mm in the same period.

Relative Risk

Sone et al (22) reported the results of aCT screening program carried out in Ja-pan in 1996–1998 that enrolled 5483subjects. They found an equal prevalence(0.5%) of lung cancer in smokers andnonsmokers, although the death ratefrom lung cancer in smokers in Japan isapproximately four times higher thanthat in nonsmokers (23). This discrep-ancy may be explained by an overdiag-nosis bias, as many of these slow-growingcancers in nonsmokers might never havebeen detected or become symptomatic ifthe subjects had not been screened. It isunclear how many of the nonsmokers inthis study may have been affected by sec-ond-hand smoke and whether this phe-nomenon, or underreporting of smokingby screening subjects, might account forthe relatively high lung cancer mortalityin nonsmokers in Japan compared withthat in the United States (24).

The relative risk for developing lungcarcinoma in male smokers was about 10times that in nonsmokers in the eightprospective studies reviewed for the 1982report of the Surgeon General on “TheHealth Consequences of Smoking” (25).For heavy smokers, the risk was 15–35times greater (25,26). Despite initial evi-dence suggesting an increased risk oflung cancer in women compared withthat in men with an equal smoking his-tory, this has not been confirmed inmore recent studies (27–30).

A history of lung cancer in first-degreerelatives is also a notable risk factor, andstrong evidence for a specific lung cancersusceptibility gene has been discoveredrecently (31,32). Other established riskfactors include exposure to asbestos, ura-nium, and radon (33–35). However, cig-arette smoke remains the overwhelm-ingly dominant culprit.

Several large screening programs arecontinuing, and we will learn more fromthese studies in the next several years.Although the available data are still in-complete, certain tentative conclusionscan be drawn at the present:

1. Approximately half of all smokersover 50 years of age have at least one lungnodule at the time of an initial screeningexamination. In addition, approximately10% of screening subjects develop a newnodule during a 1-year period (36).

2. The probability that a given nodule

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is malignant increases according to itssize (4,5). Even in smokers, the percent-age of all nodules smaller than 4 mm thatwill eventually turn into lethal cancers isvery low (�1%), whereas for those in the8-mm range the percentage is approxi-mately 10%–20% (4,7,8,37).

3. Cigarette smokers are at greater riskfor lethal cancers, and malignant nodulesin smokers grow faster, on average, thando those in nonsmokers (19,25,26). Also,the cancer risk for smokers increases inproportion to the degree and duration ofexposure to cigarette smoke (38).

4. Certain features of nodules correlatewith likelihood of malignancy, cell type,and growth rate. For instance, smallpurely ground-glass opacity (nonsolid)nodules that have malignant histopatho-logic features tend to grow very slowly,with a mean volume doubling time onthe order of 2 years (19). Solid cancers, onthe other hand, tend to grow more rap-idly, with a mean volume doubling timeon the order of 6 months. The growthrate of partly solid nodules tends to fallbetween these extremes, and this partic-ular morphologic pattern is highly pre-dictive of adenocarcinoma (39–41).

5. Increasing patient age generally cor-relates with increasing likelihood of ma-lignancy. Lung cancer is uncommon inpatients younger than 40 years and is rarein those younger than 35 years (42). Atthe other end of the age scale, althoughthe likelihood of cancer increases, surgi-cal intervention carries greater risks. Also,the likelihood of a small nodule evolvinginto a cancer that will cause prematuredeath becomes a lesser concern as comor-bidity increases in a person and predictedsurvival decreases with advancing years.

Management Approach

A number of investigators have alreadyraised serious concerns about currentmanagement strategies for the indeter-minate small nodule, particularly afterencountering an overwhelming numberof such abnormalities on CT scans(7,14,36). In the study by Henschke et al(5) described earlier, the authors foundno cancers in patients in whom the larg-est noncalcified nodule was less than 5mm in diameter on the initial scan (zeroof 378 patients). Thus there was no ad-vantage in performing short-interval fol-low-up for nodules smaller than 5 mm intheir study, even in high-risk patients.

Therefore, we recommend altering theexisting recommendations, which indi-cate that every indeterminate nodule, re-gardless of size and morphology, should

be subjected to a minimum of four or fivefollow-up CT examinations before beingdesignated benign and the patient beingreassured (1,2). As summarized above,data from ongoing CT screening pro-grams with multidetector CT with 5-mmcollimation indicate that approximatelyhalf of all smokers over 50 years of agehave at least one lung nodule on the ini-tial scan (36). In addition, approximately10% of screening subjects develop a newnodule over a 1-year period, and about12% can be expected to have one or moreadditional nodules that were missed onthe original scan (36). Assuming similardemographics, approximately 20% of pa-tients who have a nodule detected on CTscans can be expected to have at least onenew nodule detected during the cur-rently recommended 2-year minimumfollow-up period, which will in turnmandate another series of follow-up CTstudies with similar opportunities fornew nodules to be detected during theadditional follow-up period. Therefore,strict application of the existing recom-mendations would result in multiple fol-low-up studies over 2 or more years for alarge proportion of all patients who un-dergo thoracic CT.

In the case of nodules larger than 8mm, additional options such as contrastmaterial–enhanced CT, positron emis-sion tomography (PET), percutaneousneedle biopsy, and thoracoscopic resec-tion can be considered (43–46). Becausethese approaches depend greatly onavailable expertise and equipment andhave limited applicability to nodules inthe subcentimeter range, we have chosennot to offer detailed recommendations in

this regard. Rather, we have elected tofocus on the issue of follow-up imagingof smaller nodules. Specifically, for whatkinds of lesions is it appropriate to fol-low, and if followed, at what intervals?Therefore, we propose a set of guidelines,summarized in the Table, for the man-agement of small pulmonary nodules de-tected on CT scans.

Note that the recommendationsshown in the Table apply only to adultpatients with nodules that are “inciden-tal” in the sense that they are unrelatedto known underlying disease. The follow-ing examples describe patients to whomthe above guidelines would not apply.

Patients known to have or suspected ofhaving malignant disease.—Patients with acancer that may be a cause of lung me-tastases should be cared for according tothe relevant protocol or specific clinicalsituation. Pertinent factors will includethe site, cell type, and stage of the pri-mary tumor and whether early detectionof lung metastases will affect care. In thissetting, frequent follow-up CT may beindicated.

Young patients.—Primary lung cancer israre in persons under 35 years of age(�1% of all cases), and the risks fromradiation exposure are greater than in theolder population. Therefore, unless thereis a known primary cancer, multiple fol-low-up CT studies for small incidentallydetected nodules should be avoided inyoung patients. In such cases, a singlelow-dose follow-up CT scan in 6–12months should be considered.

Patients with unexplained fever.—In cer-tain clinical settings, such as a patientpresenting with neutropenic fever, the

Recommendations for Follow-up and Management of Nodules Smaller than8 mm Detected Incidentally at Nonscreening CT

Nodule Size(mm)* Low-Risk Patient† High-Risk Patient‡

�4 No follow-up needed§ Follow-up CT at 12 mo; ifunchanged, no further follow-up�

�4–6 Follow-up CT at 12 mo; ifunchanged, no further follow-up�

Initial follow-up CT at 6–12 mo thenat 18–24 mo if no change�

�6–8 Initial follow-up CT at 6–12 mo thenat 18–24 mo if no change

Initial follow-up CT at 3–6 mo thenat 9–12 and 24 mo if no change

�8 Follow-up CT at around 3, 9, and 24mo, dynamic contrast-enhancedCT, PET, and/or biopsy

Same as for low-risk patient

Note.—Newly detected indeterminate nodule in persons 35 years of age or older.* Average of length and width.† Minimal or absent history of smoking and of other known risk factors.‡ History of smoking or of other known risk factors.§ The risk of malignancy in this category (�1%) is substantially less than that in a baseline CT scan

of an asymptomatic smoker.� Nonsolid (ground-glass) or partly solid nodules may require longer follow-up to exclude

indolent adenocarcinoma.

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presence of a nodule may indicate activeinfection, and short-term imaging fol-low-up or intervention may be appropri-ate.

Previous CT scans, chest radiographs,and other pertinent imaging studiesshould be obtained for comparisonwhenever possible, as they may serve todemonstrate either stability or intervalgrowth of the nodule in question.

A low-dose, thin-section, unenhancedtechnique should be used, with limitedlongitudinal coverage, when follow-up ofa lung nodule is the only indication forthe CT examination.

DISCUSSION

Not every focal opacity qualifies as a nod-ule. Unfortunately, the familiar lungnodule has eluded all efforts at precisedefinition. A committee of the FleischnerSociety on CT nomenclature describedthe pathologic definition of a nodule as a“small, approximately spherical, circum-scribed focus of abnormal tissue” and theradiologic definition as a “round opacity,at least moderately well marginated andno greater than 3 cm in maximum diam-eter” (47). Therefore, a linear or essen-tially two-dimensional opacity that doesnot have an approximately sphericalcomponent is not a nodule. In general,purely linear or sheetlike lung opacitiesare unlikely to represent neoplasms anddo not require follow-up, even when themaximum dimension exceeds 8 mm(48).

Depending on their appearance and ra-diologic context, certain nodular opaci-ties may be judged sufficiently typical ofscarring that follow-up is not warranted.

Because at least 99% of all nodules 4mm or smaller are benign and becausesuch small opacities are extremely com-mon on thin-section CT scans, we do notrecommend follow-up CT in every suchcase; in selected cases with suspiciousmorphology or in high-risk subjects, asingle follow-up scan in 12 monthsshould be considered. We accept that thisprotocol could result in a few indolentcancers being missed, but we believe thatthe number of such instances would beextremely small relative to the reductionin the number of unnecessary studies.Given the high prevalence of small be-nign nodules, the requirement to followevery such case for a period of 2 yearsrequires vast resources. The radiationburden for the affected population is alsosubstantial, and this could be a cause ofcancer in itself (10). Finally, there is no

conclusive evidence, as yet, that serial CTstudies with early intervention for de-tected cancers can reduce disease-specificmortality, even in high-risk patients (7).Therefore, we do not recommend fol-low-up CT for every small indeterminatenodule.

Management decisions should not bebased on nodule size alone. While anycalcification in a small nodule favors abenign cause, central, laminar, or densediffuse patterns of calcification are reli-able evidence of benignancy (49). Fatcontent suggests a hamartoma or occa-sionally a lipoid granuloma or lipoma(50). Solid versus nonsolid appearance,spiculation, or other characteristics influ-ence the likelihood of malignancy andprobable growth rate in any given case(19,39,49,51,52). Longer follow-up in-tervals are appropriate for nonsolid(ground-glass opacity) and very smallopacities (19,40). For instance, even ifmalignant, a nonsolid nodule that issmaller than 6 mm will probably notgrow perceptibly in much less than 12months (19,40). Also, as discussed earlier,it has been established that accurate mea-surement of growth in subcentimeternodules is problematic (16).

Other features such as clustering ofmultiple nodules in a single location inthe lung tend to favor an infectious pro-cess, although a dominant nodule withadjacent small satellite nodules can beseen in primary lung cancer (53,54). For asingle nodule, upper lobe location in-creases the likelihood of malignancy, be-cause primary lung cancers are morecommon in the upper lobes (55). On theother hand, small, irregular, benign sub-pleural opacities, presumably due to scar-ring, are extremely common in the apicalareas in older patients, whereas triangu-lar or ovoid circumscribed nodules 3–9mm in diameter adjacent to pleural fis-sures commonly represent intrapulmo-nary lymph nodes (56). A history of can-cer can greatly increase the likelihood ofa nodule being malignant, depending onthe nature and stage of the primary neo-plasm (57).

The patient’s age and the presence ofcomorbid conditions should influencemanagement recommendations (58). Forinstance, an incidentally detected 5-mmindeterminate nodule in an 85-year-oldpatient with comorbid conditions is rel-atively unlikely to develop into a symp-tomatic lung cancer during the patient’slifetime and, therefore, does not neces-sarily require follow-up (5). However,noncalcified nodules larger than 8 mmdiameter can bear a substantial risk of

malignancy and should be managed ac-cordingly (39). Depending on the cir-cumstances, follow-up imaging studies orintervention may be appropriate. Con-servative management is generally ap-propriate for nodules in very elderly pa-tients or in those with major comorbiddisease. Interval growth of any nodulesuggests an active process, and furtherevaluation or intervention should beconsidered in such cases.

It is impossible to ignore medicolegalconsiderations when discussing manage-ment of pulmonary nodules. The currentpractice in the United States of recom-mending follow-up studies for all inde-terminate opacities is partly related toperceived liability if a cancer should de-velop (59). When the medical commu-nity has preached the importance ofearly detection of cancer for so long, itmay prove difficult to convince physi-cians and the public that follow-up CT ofevery nodule in every patient is unneces-sary. Nonetheless, it is our hope that theguidelines presented here will support apractical and medically appropriate ap-proach to the management of inciden-tally detected small pulmonary nodules.

The recommendations presented hereare based on our current understandingof pulmonary nodules, and we expectthat they will continue to evolve as moreinformation becomes available.

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