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Editorials
Radiology



            Heber MacMahon, MB,                       Guidelines for Management of
              BCh, BAO
            John H. M. Austin, MD                     Small Pulmonary Nodules
            Gordon Gamsu, MD
            Christian J. Herold, MD
            James R. Jett, MD
                                                      Detected on CT Scans:
            David P. Naidich, MD
            Edward F. Patz, Jr, MD
                                                      A Statement from the
            Stephen J. Swensen, MD
                                                      Fleischner Society1
            Published online
              10.1148/radiol.2372041887
            Radiology 2005; 237:395– 400
                                                         Lung nodules are detected very commonly on computed tomographic (CT) scans of
                                                         the chest, and the ability to detect very small nodules improves with each new
            1
              From the Department of Radiology,          generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years
            University of Chicago, 5841 S Mary-
            land Ave, MC2026, Chicago, IL 60637          or older have pulmonary nodules on CT scans. However, the existing guidelines for
            (H.M.); Department of Radiology, Co-         follow-up and management of noncalcified nodules detected on nonscreening CT
            lumbia University Medical Center,            scans were developed before widespread use of multi– detector row CT and still
            New York, NY (J.H.M.A.); Department
            of Radiology, New York Hospital, Cor-
                                                         indicate that every indeterminate nodule should be followed with serial CT for a
            nell Medical Center, New York, NY            minimum of 2 years. This policy, which requires large numbers of studies to be
            (G.G.); Department of Radiology, Uni-        performed at considerable expense and with substantial radiation exposure for the
            versity of Vienna Medical School, Vi-        affected population, has not proved to be beneficial or cost-effective. During the
            enna, Austria (C.J.H.); Departments of
            Medicine (J.R.J.) and Diagnostic Radi-       past 5 years, new information regarding prevalence, biologic characteristics, and
            ology (S.J.S.), Mayo Clinic College of       growth rates of small lung cancers has become available; thus, the authors believe
            Medicine, Rochester, Minn; Depart-           that the time-honored requirement to follow every small indeterminate nodule with
            ment of Radiology, NYU Medical Cen-
            ter, New York, NY (D.P.N.); and De-          serial CT should be revised. In this statement, which has been approved by the
            partment of Radiology, Duke Univer-          Fleischner Society, the pertinent data are reviewed, the authors’ conclusions are
            sity Medical Center, Durham, NC              summarized, and new guidelines are proposed for follow-up and management of
            (E.F.P.). Received November 5, 2004;
                                                         small pulmonary nodules detected on CT scans.
            revision requested January 5, 2005; re-
                                                         ©
            vision received March 3; accepted May            RSNA, 2005
            2. Address correspondence to H.M.
            (e-mail: macm@midway.uchicago.edu).
            ©   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 proved
                                                      stable over a period of 2 years (1,2). This approach was adopted prior to the widespread use
                                                      of computed tomography (CT) and was based on the observation that a substantial
                                                      proportion of noncalcified nodules that were detected at chest radiography turned out to
                                                      be lung cancers. These nodules were almost all larger than 5 mm in diameter, and most
                                                      were in the 1–3-cm range.
                                                         Since the introduction of helical CT in the early 1990s and multi– detector row CT in the
                                                      late 1990s, the detection of focal rounded pulmonary opacities (“nodules”) as small as 1–2
                                                      mm in diameter has become routine. In fact, the majority of smokers who undergo
                                                      thin-section CT have been found to have small lung nodules, most of which are smaller
                                                      than 7 mm in diameter (3). However, the clinical importance of these extremely small
                                                      nodules differs substantially from that of larger nodules detected on chest radiographs, in
                                                      that the vast majority are benign. This issue has been highlighted in several recent
                                                      publications on CT screening for lung cancer, and the positive relationship of lesion size
                                                      to likelihood of malignancy has been clearly demonstrated (4,5).
                                                         The only current guidelines in the radiology literature for management of small nodules
                                                      are 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 are
                                                      selected on the basis of age, substantial smoking history, absence of serious comorbid
                                                      disease, 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-


                                                                                                                                              395
tion, with a view to achieving the highest    nodule that would qualify for this proto-     CT. If the nodule did not exhibit un-
            possible cure rate while gaining further      col (2).                                      equivocally benign characteristics (be-
            insight into the behavior and character-         The rationale for recommending serial      nign pattern of calcification, smooth
            istics of small malignant lesions. There-     follow-up studies for all indeterminate       margins, and size less than 20 mm), it
            fore, patients whose nodules are detected     small nodules is that some of them will       was followed up with thin-section CT at
Radiology



            incidentally during the course of CT per-     turn out to be cancers and that early in-     3 months and subsequently at 6, 12, and
            formed for other reasons should not nec-      tervention will provide an opportunity        24 months in the absence of change.
            essarily be treated in the same way as        for cure. The “downside” of this policy       Only one cancer was less than 5 mm in
            subjects in a screening program. Nonethe-     includes potential morbidity and mor-         diameter at the time of detection in the
            less, although CT screening has not as yet    tality from surgery for benign nodules        baseline (10-mm-collimation) study. The
            been proved to help reduce mortality from     and other false-positive findings, poor        results of the repeat screening were re-
            lung cancer, these programs provide an        utilization of limited resources, in-         ported in 2001. Seven new cancers were
            important source of information for deter-    creased health care costs, unnecessary        detected at the repeat screening; three of
            mining the optimal management of “inci-       patient anxiety, loss of credibility for      these were 5 mm in size (defined as the
            dental” nodules detected in other situa-      radiologists who may seem to recom-           average of the length and width in that
            tions.                                        mend excessive numbers of CT scans            study); all the other proved cancers were
               Our intent in this position statement is   with little benefit, and increased radia-      larger (8).
            to provide practical guidelines for the       tion burden for the affected popula-             Swensen et al (7) reported the results of
            management of small pulmonary nod-            tion. The radiation issue is particularly     the Mayo Clinic Lung Cancer Screening
            ules that are detected during the course      important in younger patients and             Trial after completion of three annual
            of CT examinations performed for pur-         must be taken into account in deter-          low-dose CT examinations in 1520 smok-
            poses other than lung cancer screening.       mining appropriate follow-up strategies       ers. The subjects were aged 50 years or
            We recognize that this issue is complex       (10 –13).                                     older and had a smoking history of 20
            and difficult to reduce to a simple algo-         There remains a growing need to reex-      pack-years or more. Two years after base-
            rithm. We also realize that the definition     amine the radiologic approach to small        line screening, 2832 noncalcified pulmo-
            of a pulmonary nodule is itself elusive,      nodules, particularly when CT is per-
                                                                                                        nary nodules had been identified in 1049
            and that not all focal opacities qualify as   formed for indications other than screen-
                                                                                                        (69%) participants. Thirty-six lung can-
            nodules. Yet, we believe that there is a      ing. Several fundamental issues need to
                                                                                                        cers were diagnosed with the aid of CT
            practical need in the medical community       be considered before an imaging strategy
                                                                                                        (2.6% of participants, 1.4% of nodules):
            for guidance in this area.                    is recommended. Since the decision to
                                                                                                        26 at baseline (prevalence) and 10 at sub-
                                                          perform follow-up studies relies on size,
                                                                                                        sequent annual (incidence) CT examina-
                                                          lesion characteristics (eg, morphology),
            BACKGROUND                                                                                  tions. Thirty-two (80%) of these cancers
                                                          and growth rates (typically described as
                                                                                                        were larger than 8 mm, and only one was
                                                          doubling time), an understanding of
                                                                                                        smaller than 5 mm at the time of detec-
            Available data indicate that fewer than       these features and their relationship to
                                                                                                        tion. Two cancers were detected by using
            1% of very small ( 5-mm) nodules in           malignancy should dictate further evalu-
                                                                                                        sputum cytology, and there were two in-
            patients without a history of cancer will     ation. In addition, the patient’s risk pro-
                                                                                                        terval cancers.
            demonstrate malignant behavior (ie, de-       file, including age and smoking history,
            tectable growth or metastases over a pe-      needs to be integrated into the diagnostic       Benjamin et al (14) reported the results
            riod of 2 or more years) (5,7,9). Nonethe-    algorithm.                                    of a retrospective review of 334 non-
            less, multiple follow-up examinations                                                       screening cases in which a lung nodule or
            over a 2-year period are commonly per-                                                      nodules were detected that were less than
                                                          Nodules Detected on CT Scans                  10 mm in their long axis and for which
            formed when such nodules are detected
            incidentally. Guidelines for the manage-         During the past 5 years, new informa-      follow-up CT was recommended. These
            ment of the solitary pulmonary nodule         tion regarding the morphology, biologic       nodules were identified from 3446 con-
            were published in 2003 by the American        characteristics, and growth rates of small    secutive chest CT studies performed at
            College of Chest Physicians (2) and in a      lung cancers has become available from        their institution. Among patients with a
            review in by Ost and colleagues in the        CT lung cancer screening programs             nodule, 87 patients had “definitive” fol-
            New England Journal of Medicine (1). How-     throughout the world. Selected studies        low-up results (2 years without change or
            ever, neither of these articles specifically   are summarized below as representative        biopsy). Nodules in 10 (11%) of these
            addressed the issue of the very small nod-    of the present state of knowledge in this     patients were malignant. Nine of these
            ule that is detected as an incidental find-    area.                                         cases were metastases from known pri-
            ing on a CT scan. Ost and colleagues con-        Henschke et al (9) published the initial   mary tumors, and one turned out to be a
            cluded by recommending CT follow-up           results from the Early Lung Cancer Ac-        metastasis from an occult primary tumor.
            at 3, 6, 12, 18, and 24 months for all        tion Project CT screening project in 1999.    This high incidence of metastases is a
            “low-probability” indeterminate nodules       They enrolled 1000 asymptomatic smok-         reflection of the patient population that
            (ie, nodules with a low likelihood of be-     ers or ex-smokers with at least 10 pack-      was used for this study, in that 56% of
            ing cancer), regardless of size (1). The      years of cigarette smoking who were aged      the included patients had a known pri-
            American College of Chest Physicians          60 years or older. Screening CT studies       mary tumor. The authors of that article
            recommendation for management of in-          were performed with 10-mm collima-            suggested that the malignancy rate in
            determinate solitary nodules was similar,     tion. The investigators found noncalci-       small nodules in patients without a
            with the proposal for 3-, 6-, 12-, and 24-    fied nodules in 23% of subjects and ma-        known neoplasm may be as low as 1%
            month CT follow-up intervals, also with-      lignant nodules in 2.7%. All detected         and that follow-up may not be necessary
            out any specified lower size limit for a       nodules were subjected to thin-section        in such cases.

            396   Radiology   November 2005                                                                                         MacMahon et al
Nodule Size                                   pers, or software that performs auto-         diameter of 20.3 mm in 12 months,
                                                          mated volumetric measurement of the           whereas a similar nodule with a doubling
               On the basis of analysis of information
                                                          nodule (15). The minified display used         time of 240 days would reach a diameter
            from the ongoing Mayo Clinic CT
                                                          for hard copy makes accurate measure-         of only 7.1 mm in the same period.
            Screening Trial, Midthun et al (4) re-
                                                          ment of subcentimeter nodules virtually
            ported that fewer than 1% of very small
Radiology



                                                          impossible. Even with a state-of-the-art
            ( 5-mm) nodules in patients without a                                                       Relative Risk
                                                          soft-copy display and electronic calipers,
            history of cancer were malignant. They
                                                          substantial inter- and intrareader varia-        Sone et al (22) reported the results of a
            indicated a likelihood of malignancy of
                                                          tions in two-dimensional measurements         CT screening program carried out in Ja-
            0.2% for nodules smaller than 3 mm,
                                                          have been documented (16). Revel and          pan in 1996 –1998 that enrolled 5483
            0.9% for those 4 –7 mm, 18% for those         colleagues (16) determined that two-di-       subjects. They found an equal prevalence
            8 –20 mm, and 50% for those larger than       mensional measurements obtained with          (0.5%) of lung cancer in smokers and
            20 mm.                                        electronic calipers were unreliable as a      nonsmokers, although the death rate
               Henschke and colleagues (5) recently       basis for distinguishing benign from ma-      from lung cancer in smokers in Japan is
            addressed the issue of optimal follow-up      lignant solid nodules in the 5–15-mm          approximately four times higher than
            intervals for nodules smaller than 5 mm       size range. Limited studies (15,17) that      that in nonsmokers (23). This discrep-
            in diameter. They performed a retrospec-      have been performed with automated            ancy may be explained by an overdiag-
            tive review of a total of 2897 baseline       three-dimensional analysis suggest that       nosis bias, as many of these slow-growing
            screening studies performed between           such systems can be considerably more         cancers in nonsmokers might never have
            1993 and 2002 in order to identify those      accurate and consistent than unaided          been detected or become symptomatic if
            subjects with noncalcified nodules that,       radiologists in determining interval          the subjects had not been screened. It is
            at initial detection, were (a) smaller than   changes in small nodules. However, Kos-       unclear how many of the nonsmokers in
            5 mm in diameter and (b) 5–9 mm in            tis and colleagues (18) have shown that       this study may have been affected by sec-
            diameter. In accordance with the screen-      even sophisticated automated volume-          ond-hand smoke and whether this phe-
            ing program guidelines, indeterminate         measurement methods are susceptible to        nomenon, or underreporting of smoking
            nodules were rescanned at 3-, 6-, and 12-     errors due to motion artifacts or segmen-     by screening subjects, might account for
            month intervals, while some in the            tation problems, particularly in the case     the relatively high lung cancer mortality
            5–9-mm range that had particularly sus-       of very small nodules.                        in nonsmokers in Japan compared with
            picious morphology were recommended                                                         that in the United States (24).
            for biopsy. On the basis of the results of                                                     The relative risk for developing lung
            these follow-up studies and biopsies, the     Growth Rate
                                                                                                        carcinoma in male smokers was about 10
            authors determined that when the largest         Hasegawa et al (19) reported an analy-     times that in nonsmokers in the eight
            noncalcified nodule was smaller than 5         sis of the growth rates of small lung can-    prospective studies reviewed for the 1982
            mm in diameter (378 patients), a fol-         cers detected during a 3-year mass screen-    report of the Surgeon General on “The
            low-up study in 12 months would have          ing program. They classified nodules as        Health Consequences of Smoking” (25).
            resulted in no case of delayed diagnosis,     ground-glass opacity, as ground-glass         For heavy smokers, the risk was 15–35
            compared with more aggressive short-          opacity with a solid component, or as         times greater (25,26). Despite initial evi-
            term follow-up. However, when the larg-       solid. Mean volume doubling times were        dence suggesting an increased risk of
            est nodule was 5–9 mm in diameter, ap-        813 days, 457 days, and 149 days, respec-     lung cancer in women compared with
            proximately 6% of cases (all of which         tively, for these three types, all of which   that in men with an equal smoking his-
            were malignant) showed interval nodule        were significantly different. In addition,     tory, this has not been confirmed in
            growth detectable on 4 – 8-month fol-         the mean volume doubling time for can-        more recent studies (27–30).
            low-up scans. Therefore, they recom-          cerous nodules in nonsmokers was signif-         A history of lung cancer in first-degree
            mended that patients with nodules no          icantly longer than that for cancerous        relatives is also a notable risk factor, and
            larger than 5 mm in diameter on a base-       nodules in smokers. The mean volume           strong evidence for a specific lung cancer
            line screening CT scan should be referred     doubling time was also significantly           susceptibility gene has been discovered
            for repeat annual screening in 12 months      longer for nodules not visible on chest       recently (31,32). Other established risk
            time, with no interval scans. This recom-     radiographs (presumably a function of         factors include exposure to asbestos, ura-
            mendation differs only slightly from the      their smaller average size and/or their       nium, and radon (33–35). However, cig-
            current protocol for the ongoing Na-          lesser average opacity). These data further   arette smoke remains the overwhelm-
            tional Lung Screening Trial, in which pa-     support the use of extended follow-up         ingly dominant culprit.
            tients with nodules smaller than 4 mm in      intervals for small nonsolid or partly           Several large screening programs are
            diameter are recommended to return for        solid nodules, even in high-risk patients.    continuing, and we will learn more from
            screening after 12 months, without inter-     Authors of a number of other series           these studies in the next several years.
            val scans or other work-up. Note that         (20,21) have confirmed similar findings         Although the available data are still in-
            these recommendations refer to high-risk      and have estimated the median tumor           complete, certain tentative conclusions
            subjects who have enrolled in a screening     doubling times, assuming a constant           can be drawn at the present:
            program.                                      growth rate to be in the 160 –180-day            1. Approximately half of all smokers
               A further practical issue arises in the    range. Authors of all of these reports,       over 50 years of age have at least one lung
            follow-up to detect interval growth of        however, recognize wide variations, and       nodule at the time of an initial screening
            very small nodules. Comparison of cur-        in one study 22% of tumors had a vol-         examination. In addition, approximately
            rent and previous scans can be performed      ume doubling time of 465 days or more         10% of screening subjects develop a new
            by using hard copy with manual mea-           (21). Note that a 5-mm nodule with a          nodule during a 1-year period (36).
            surement, soft copy with electronic cali-     doubling time of 60 days will reach a            2. The probability that a given nodule

            Volume 237   Number 2                                               Fleischner Society Statement on CT of Small Pulmonary Nodules   397
is malignant increases according to its
            size (4,5). Even in smokers, the percent-        Recommendations for Follow-up and Management of Nodules Smaller than
                                                             8 mm Detected Incidentally at Nonscreening CT
            age of all nodules smaller than 4 mm that
            will eventually turn into lethal cancers is      Nodule Size
            very low ( 1%), whereas for those in the           (mm)*                      Low-Risk Patient†                           High-Risk Patient‡
Radiology



            8-mm range the percentage is approxi-                 4            No follow-up needed    §
                                                                                                                            Follow-up CT at 12 mo; if
            mately 10%–20% (4,7,8,37).                                                                                         unchanged, no further follow-up
               3. Cigarette smokers are at greater risk           4–6          Follow-up CT at 12 mo; if                    Initial follow-up CT at 6–12 mo then
            for lethal cancers, and malignant nodules                             unchanged, no further follow-up              at 18–24 mo if no change
                                                                  6–8          Initial follow-up CT at 6–12 mo then         Initial follow-up CT at 3–6 mo then
            in smokers grow faster, on average, than                              at 18–24 mo if no change                     at 9–12 and 24 mo if no change
            do those in nonsmokers (19,25,26). Also,              8            Follow-up CT at around 3, 9, and 24          Same as for low-risk patient
            the cancer risk for smokers increases in                              mo, dynamic contrast-enhanced
            proportion to the degree and duration of                              CT, PET, and/or biopsy
            exposure to cigarette smoke (38).                Note.—Newly detected indeterminate nodule in persons 35 years of age or older.
               4. Certain features of nodules correlate        * Average of length and width.
                                                               † Minimal or absent history of smoking and of other known risk factors.
            with likelihood of malignancy, cell type,          ‡ History of smoking or of other known risk factors.
            and growth rate. For instance, small               §
                                                                 The risk of malignancy in this category ( 1%) is substantially less than that in a baseline CT scan
            purely ground-glass opacity (nonsolid)           of an asymptomatic smoker.
            nodules that have malignant histopatho-              Nonsolid (ground-glass) or partly solid nodules may require longer follow-up to exclude
            logic features tend to grow very slowly,         indolent adenocarcinoma.
            with a mean volume doubling time on
            the order of 2 years (19). Solid cancers, on
            the other hand, tend to grow more rap-
            idly, with a mean volume doubling time          be subjected to a minimum of four or five              this regard. Rather, we have elected to
            on the order of 6 months. The growth            follow-up CT examinations before being                focus on the issue of follow-up imaging
            rate of partly solid nodules tends to fall      designated benign and the patient being               of smaller nodules. Specifically, for what
            between these extremes, and this partic-        reassured (1,2). As summarized above,                 kinds of lesions is it appropriate to fol-
            ular morphologic pattern is highly pre-         data from ongoing CT screening pro-                   low, and if followed, at what intervals?
            dictive of adenocarcinoma (39 – 41).            grams with multidetector CT with 5-mm                 Therefore, we propose a set of guidelines,
               5. Increasing patient age generally cor-     collimation indicate that approximately               summarized in the Table, for the man-
            relates with increasing likelihood of ma-       half of all smokers over 50 years of age              agement of small pulmonary nodules de-
            lignancy. Lung cancer is uncommon in            have at least one lung nodule on the ini-             tected on CT scans.
            patients younger than 40 years and is rare      tial scan (36). In addition, approximately               Note that the recommendations
            in those younger than 35 years (42). At         10% of screening subjects develop a new               shown in the Table apply only to adult
            the other end of the age scale, although        nodule over a 1-year period, and about                patients with nodules that are “inciden-
            the likelihood of cancer increases, surgi-      12% can be expected to have one or more               tal” in the sense that they are unrelated
            cal intervention carries greater risks. Also,   additional nodules that were missed on                to known underlying disease. The follow-
            the likelihood of a small nodule evolving       the original scan (36). Assuming similar              ing examples describe patients to whom
            into a cancer that will cause premature         demographics, approximately 20% of pa-                the above guidelines would not apply.
            death becomes a lesser concern as comor-        tients who have a nodule detected on CT                  Patients known to have or suspected of
            bidity increases in a person and predicted      scans can be expected to have at least one            having malignant disease.—Patients with a
            survival decreases with advancing years.        new nodule detected during the cur-                   cancer that may be a cause of lung me-
                                                            rently recommended 2-year minimum                     tastases should be cared for according to
                                                            follow-up period, which will in turn                  the relevant protocol or specific clinical
            Management Approach
                                                            mandate another series of follow-up CT                situation. Pertinent factors will include
               A number of investigators have already       studies with similar opportunities for                the site, cell type, and stage of the pri-
            raised serious concerns about current           new nodules to be detected during the                 mary tumor and whether early detection
            management strategies for the indeter-          additional follow-up period. Therefore,               of lung metastases will affect care. In this
            minate small nodule, particularly after         strict application of the existing recom-             setting, frequent follow-up CT may be
            encountering an overwhelming number             mendations would result in multiple fol-              indicated.
            of such abnormalities on CT scans               low-up studies over 2 or more years for a                Young patients.—Primary lung cancer is
            (7,14,36). In the study by Henschke et al       large proportion of all patients who un-              rare in persons under 35 years of age
            (5) described earlier, the authors found        dergo thoracic CT.                                    ( 1% of all cases), and the risks from
            no cancers in patients in whom the larg-           In the case of nodules larger than 8               radiation exposure are greater than in the
            est noncalcified nodule was less than 5          mm, additional options such as contrast               older population. Therefore, unless there
            mm in diameter on the initial scan (zero        material– enhanced CT, positron emis-                 is a known primary cancer, multiple fol-
            of 378 patients). Thus there was no ad-         sion tomography (PET), percutaneous                   low-up CT studies for small incidentally
            vantage in performing short-interval fol-       needle biopsy, and thoracoscopic resec-               detected nodules should be avoided in
            low-up for nodules smaller than 5 mm in         tion can be considered (43– 46). Because              young patients. In such cases, a single
            their study, even in high-risk patients.        these approaches depend greatly on                    low-dose follow-up CT scan in 6 –12
               Therefore, we recommend altering the         available expertise and equipment and                 months should be considered.
            existing recommendations, which indi-           have limited applicability to nodules in                 Patients with unexplained fever.—In cer-
            cate that every indeterminate nodule, re-       the subcentimeter range, we have chosen               tain clinical settings, such as a patient
            gardless of size and morphology, should         not to offer detailed recommendations in              presenting with neutropenic fever, the

            398   Radiology   November 2005                                                                                                        MacMahon et al
presence of a nodule may indicate active      conclusive evidence, as yet, that serial CT   malignancy and should be managed ac-
            infection, and short-term imaging fol-        studies with early intervention for de-       cordingly (39). Depending on the cir-
            low-up or intervention may be appropri-       tected cancers can reduce disease-specific     cumstances, follow-up imaging studies or
            ate.                                          mortality, even in high-risk patients (7).    intervention may be appropriate. Con-
               Previous CT scans, chest radiographs,      Therefore, we do not recommend fol-           servative management is generally ap-
            and other pertinent imaging studies           low-up CT for every small indeterminate
Radiology



                                                                                                        propriate for nodules in very elderly pa-
            should be obtained for comparison             nodule.                                       tients or in those with major comorbid
            whenever possible, as they may serve to          Management decisions should not be         disease. Interval growth of any nodule
            demonstrate either stability or interval      based on nodule size alone. While any         suggests an active process, and further
            growth of the nodule in question.             calcification in a small nodule favors a       evaluation or intervention should be
               A low-dose, thin-section, unenhanced       benign cause, central, laminar, or dense      considered in such cases.
            technique should be used, with limited        diffuse patterns of calcification are reli-       It is impossible to ignore medicolegal
            longitudinal coverage, when follow-up of      able evidence of benignancy (49). Fat         considerations when discussing manage-
            a lung nodule is the only indication for      content suggests a hamartoma or occa-         ment of pulmonary nodules. The current
            the CT examination.                           sionally a lipoid granuloma or lipoma         practice in the United States of recom-
                                                          (50). Solid versus nonsolid appearance,       mending follow-up studies for all inde-
                                                          spiculation, or other characteristics influ-   terminate opacities is partly related to
            DISCUSSION                                    ence the likelihood of malignancy and         perceived liability if a cancer should de-
                                                          probable growth rate in any given case        velop (59). When the medical commu-
            Not every focal opacity qualifies as a nod-    (19,39,49,51,52). Longer follow-up in-        nity has preached the importance of
            ule. Unfortunately, the familiar lung         tervals are appropriate for nonsolid          early detection of cancer for so long, it
            nodule has eluded all efforts at precise      (ground-glass opacity) and very small         may prove difficult to convince physi-
            definition. A committee of the Fleischner      opacities (19,40). For instance, even if      cians and the public that follow-up CT of
            Society on CT nomenclature described          malignant, a nonsolid nodule that is          every nodule in every patient is unneces-
            the pathologic definition of a nodule as a     smaller than 6 mm will probably not           sary. Nonetheless, it is our hope that the
            “small, approximately spherical, circum-      grow perceptibly in much less than 12         guidelines presented here will support a
            scribed focus of abnormal tissue” and the     months (19,40). Also, as discussed earlier,   practical and medically appropriate ap-
            radiologic definition as a “round opacity,     it has been established that accurate mea-    proach to the management of inciden-
            at least moderately well marginated and       surement of growth in subcentimeter           tally detected small pulmonary nodules.
            no greater than 3 cm in maximum diam-         nodules is problematic (16).                     The recommendations presented here
            eter” (47). Therefore, a linear or essen-        Other features such as clustering of       are based on our current understanding
            tially two-dimensional opacity that does      multiple nodules in a single location in      of pulmonary nodules, and we expect
            not have an approximately spherical           the lung tend to favor an infectious pro-     that they will continue to evolve as more
            component is not a nodule. In general,        cess, although a dominant nodule with         information becomes available.
            purely linear or sheetlike lung opacities     adjacent small satellite nodules can be
            are unlikely to represent neoplasms and       seen in primary lung cancer (53,54). For a
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Spn ct radiology

  • 1. Editorials Radiology Heber MacMahon, MB, Guidelines for Management of BCh, BAO John H. M. Austin, MD Small Pulmonary Nodules Gordon Gamsu, MD Christian J. Herold, MD James R. Jett, MD Detected on CT Scans: David P. Naidich, MD Edward F. Patz, Jr, MD A Statement from the Stephen J. Swensen, MD Fleischner Society1 Published online 10.1148/radiol.2372041887 Radiology 2005; 237:395– 400 Lung nodules are detected very commonly on computed tomographic (CT) scans of the chest, and the ability to detect very small nodules improves with each new 1 From the Department of Radiology, generation of CT scanner. In reported studies, up to 51% of smokers aged 50 years University of Chicago, 5841 S Mary- land Ave, MC2026, Chicago, IL 60637 or older have pulmonary nodules on CT scans. However, the existing guidelines for (H.M.); Department of Radiology, Co- follow-up and management of noncalcified nodules detected on nonscreening CT lumbia University Medical Center, scans were developed before widespread use of multi– detector row CT and still New York, NY (J.H.M.A.); Department of Radiology, New York Hospital, Cor- indicate that every indeterminate nodule should be followed with serial CT for a nell Medical Center, New York, NY minimum of 2 years. This policy, which requires large numbers of studies to be (G.G.); Department of Radiology, Uni- performed at considerable expense and with substantial radiation exposure for the versity of Vienna Medical School, Vi- affected population, has not proved to be beneficial or cost-effective. During the enna, Austria (C.J.H.); Departments of Medicine (J.R.J.) and Diagnostic Radi- past 5 years, new information regarding prevalence, biologic characteristics, and ology (S.J.S.), Mayo Clinic College of growth rates of small lung cancers has become available; thus, the authors believe Medicine, Rochester, Minn; Depart- that the time-honored requirement to follow every small indeterminate nodule with ment of Radiology, NYU Medical Cen- ter, New York, NY (D.P.N.); and De- serial CT should be revised. In this statement, which has been approved by the partment of Radiology, Duke Univer- Fleischner Society, the pertinent data are reviewed, the authors’ conclusions are sity Medical Center, Durham, NC summarized, and new guidelines are proposed for follow-up and management of (E.F.P.). Received November 5, 2004; small pulmonary nodules detected on CT scans. revision requested January 5, 2005; re- © vision received March 3; accepted May RSNA, 2005 2. Address correspondence to H.M. (e-mail: macm@midway.uchicago.edu). © 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 proved stable over a period of 2 years (1,2). This approach was adopted prior to the widespread use of computed tomography (CT) and was based on the observation that a substantial proportion of noncalcified nodules that were detected at chest radiography turned out to be lung cancers. These nodules were almost all larger than 5 mm in diameter, and most were in the 1–3-cm range. Since the introduction of helical CT in the early 1990s and multi– detector row CT in the late 1990s, the detection of focal rounded pulmonary opacities (“nodules”) as small as 1–2 mm in diameter has become routine. In fact, the majority of smokers who undergo thin-section CT have been found to have small lung nodules, most of which are smaller than 7 mm in diameter (3). However, the clinical importance of these extremely small nodules differs substantially from that of larger nodules detected on chest radiographs, in that the vast majority are benign. This issue has been highlighted in several recent publications on CT screening for lung cancer, and the positive relationship of lesion size to likelihood of malignancy has been clearly demonstrated (4,5). The only current guidelines in the radiology literature for management of small nodules are 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 are selected on the basis of age, substantial smoking history, absence of serious comorbid disease, 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- 395
  • 2. tion, with a view to achieving the highest nodule that would qualify for this proto- CT. If the nodule did not exhibit un- possible cure rate while gaining further col (2). equivocally benign characteristics (be- insight into the behavior and character- The rationale for recommending serial nign pattern of calcification, smooth istics of small malignant lesions. There- follow-up studies for all indeterminate margins, and size less than 20 mm), it fore, patients whose nodules are detected small nodules is that some of them will was followed up with thin-section CT at Radiology incidentally during the course of CT per- turn out to be cancers and that early in- 3 months and subsequently at 6, 12, and formed for other reasons should not nec- tervention will provide an opportunity 24 months in the absence of change. essarily be treated in the same way as for cure. The “downside” of this policy Only one cancer was less than 5 mm in subjects in a screening program. Nonethe- includes potential morbidity and mor- diameter at the time of detection in the less, although CT screening has not as yet tality from surgery for benign nodules baseline (10-mm-collimation) study. The been proved to help reduce mortality from and other false-positive findings, poor results of the repeat screening were re- lung cancer, these programs provide an utilization of limited resources, in- ported in 2001. Seven new cancers were important source of information for deter- creased health care costs, unnecessary detected at the repeat screening; three of mining the optimal management of “inci- patient anxiety, loss of credibility for these were 5 mm in size (defined as the dental” nodules detected in other situa- radiologists who may seem to recom- average of the length and width in that tions. mend excessive numbers of CT scans study); all the other proved cancers were Our intent in this position statement is with little benefit, and increased radia- larger (8). to provide practical guidelines for the tion burden for the affected popula- Swensen et al (7) reported the results of management of small pulmonary nod- tion. The radiation issue is particularly the Mayo Clinic Lung Cancer Screening ules that are detected during the course important in younger patients and Trial after completion of three annual of CT examinations performed for pur- must be taken into account in deter- low-dose CT examinations in 1520 smok- poses other than lung cancer screening. mining appropriate follow-up strategies ers. The subjects were aged 50 years or We recognize that this issue is complex (10 –13). older and had a smoking history of 20 and difficult to reduce to a simple algo- There remains a growing need to reex- pack-years or more. Two years after base- rithm. We also realize that the definition amine the radiologic approach to small line screening, 2832 noncalcified pulmo- of a pulmonary nodule is itself elusive, nodules, particularly when CT is per- nary nodules had been identified in 1049 and that not all focal opacities qualify as formed for indications other than screen- (69%) participants. Thirty-six lung can- nodules. Yet, we believe that there is a ing. Several fundamental issues need to cers were diagnosed with the aid of CT practical need in the medical community be considered before an imaging strategy (2.6% of participants, 1.4% of nodules): for guidance in this area. is recommended. Since the decision to 26 at baseline (prevalence) and 10 at sub- perform follow-up studies relies on size, sequent annual (incidence) CT examina- lesion characteristics (eg, morphology), BACKGROUND tions. Thirty-two (80%) of these cancers and growth rates (typically described as were larger than 8 mm, and only one was doubling time), an understanding of smaller than 5 mm at the time of detec- Available data indicate that fewer than these features and their relationship to tion. Two cancers were detected by using 1% of very small ( 5-mm) nodules in malignancy should dictate further evalu- sputum cytology, and there were two in- patients without a history of cancer will ation. In addition, the patient’s risk pro- terval cancers. demonstrate malignant behavior (ie, de- file, including age and smoking history, tectable growth or metastases over a pe- needs to be integrated into the diagnostic Benjamin et al (14) reported the results riod of 2 or more years) (5,7,9). Nonethe- algorithm. of a retrospective review of 334 non- less, multiple follow-up examinations screening cases in which a lung nodule or over a 2-year period are commonly per- nodules were detected that were less than Nodules Detected on CT Scans 10 mm in their long axis and for which formed when such nodules are detected incidentally. Guidelines for the manage- During the past 5 years, new informa- follow-up CT was recommended. These ment of the solitary pulmonary nodule tion regarding the morphology, biologic nodules were identified from 3446 con- were published in 2003 by the American characteristics, and growth rates of small secutive chest CT studies performed at College of Chest Physicians (2) and in a lung cancers has become available from their institution. Among patients with a review in by Ost and colleagues in the CT lung cancer screening programs nodule, 87 patients had “definitive” fol- New England Journal of Medicine (1). How- throughout the world. Selected studies low-up results (2 years without change or ever, neither of these articles specifically are summarized below as representative biopsy). Nodules in 10 (11%) of these addressed the issue of the very small nod- of the present state of knowledge in this patients were malignant. Nine of these ule that is detected as an incidental find- area. cases were metastases from known pri- ing on a CT scan. Ost and colleagues con- Henschke et al (9) published the initial mary tumors, and one turned out to be a cluded by recommending CT follow-up results from the Early Lung Cancer Ac- metastasis from an occult primary tumor. at 3, 6, 12, 18, and 24 months for all tion Project CT screening project in 1999. This high incidence of metastases is a “low-probability” indeterminate nodules They enrolled 1000 asymptomatic smok- reflection of the patient population that (ie, nodules with a low likelihood of be- ers or ex-smokers with at least 10 pack- was used for this study, in that 56% of ing cancer), regardless of size (1). The years of cigarette smoking who were aged the included patients had a known pri- American College of Chest Physicians 60 years or older. Screening CT studies mary tumor. The authors of that article recommendation for management of in- were performed with 10-mm collima- suggested that the malignancy rate in determinate solitary nodules was similar, tion. The investigators found noncalci- small nodules in patients without a with the proposal for 3-, 6-, 12-, and 24- fied nodules in 23% of subjects and ma- known neoplasm may be as low as 1% month CT follow-up intervals, also with- lignant nodules in 2.7%. All detected and that follow-up may not be necessary out any specified lower size limit for a nodules were subjected to thin-section in such cases. 396 Radiology November 2005 MacMahon et al
  • 3. Nodule Size pers, or software that performs auto- diameter of 20.3 mm in 12 months, mated volumetric measurement of the whereas a similar nodule with a doubling On the basis of analysis of information nodule (15). The minified display used time of 240 days would reach a diameter from the ongoing Mayo Clinic CT for hard copy makes accurate measure- of only 7.1 mm in the same period. Screening Trial, Midthun et al (4) re- ment of subcentimeter nodules virtually ported that fewer than 1% of very small Radiology impossible. Even with a state-of-the-art ( 5-mm) nodules in patients without a Relative Risk soft-copy display and electronic calipers, history of cancer were malignant. They substantial inter- and intrareader varia- Sone et al (22) reported the results of a indicated a likelihood of malignancy of tions in two-dimensional measurements CT screening program carried out in Ja- 0.2% for nodules smaller than 3 mm, have been documented (16). Revel and pan in 1996 –1998 that enrolled 5483 0.9% for those 4 –7 mm, 18% for those colleagues (16) determined that two-di- subjects. They found an equal prevalence 8 –20 mm, and 50% for those larger than mensional measurements obtained with (0.5%) of lung cancer in smokers and 20 mm. electronic calipers were unreliable as a nonsmokers, although the death rate Henschke and colleagues (5) recently basis for distinguishing benign from ma- from lung cancer in smokers in Japan is addressed the issue of optimal follow-up lignant solid nodules in the 5–15-mm approximately four times higher than intervals for nodules smaller than 5 mm size range. Limited studies (15,17) that that in nonsmokers (23). This discrep- in diameter. They performed a retrospec- have been performed with automated ancy may be explained by an overdiag- tive review of a total of 2897 baseline three-dimensional analysis suggest that nosis bias, as many of these slow-growing screening studies performed between such systems can be considerably more cancers in nonsmokers might never have 1993 and 2002 in order to identify those accurate and consistent than unaided been detected or become symptomatic if subjects with noncalcified nodules that, radiologists in determining interval the subjects had not been screened. It is at initial detection, were (a) smaller than changes in small nodules. However, Kos- unclear how many of the nonsmokers in 5 mm in diameter and (b) 5–9 mm in tis and colleagues (18) have shown that this study may have been affected by sec- diameter. In accordance with the screen- even sophisticated automated volume- ond-hand smoke and whether this phe- ing program guidelines, indeterminate measurement methods are susceptible to nomenon, or underreporting of smoking nodules were rescanned at 3-, 6-, and 12- errors due to motion artifacts or segmen- by screening subjects, might account for month intervals, while some in the tation problems, particularly in the case the relatively high lung cancer mortality 5–9-mm range that had particularly sus- of very small nodules. in nonsmokers in Japan compared with picious morphology were recommended that in the United States (24). for biopsy. On the basis of the results of The relative risk for developing lung these follow-up studies and biopsies, the Growth Rate carcinoma in male smokers was about 10 authors determined that when the largest Hasegawa et al (19) reported an analy- times that in nonsmokers in the eight noncalcified nodule was smaller than 5 sis of the growth rates of small lung can- prospective studies reviewed for the 1982 mm in diameter (378 patients), a fol- cers detected during a 3-year mass screen- report of the Surgeon General on “The low-up study in 12 months would have ing program. They classified nodules as Health Consequences of Smoking” (25). resulted in no case of delayed diagnosis, ground-glass opacity, as ground-glass For heavy smokers, the risk was 15–35 compared with more aggressive short- opacity with a solid component, or as times greater (25,26). Despite initial evi- term follow-up. However, when the larg- solid. Mean volume doubling times were dence suggesting an increased risk of est nodule was 5–9 mm in diameter, ap- 813 days, 457 days, and 149 days, respec- lung cancer in women compared with proximately 6% of cases (all of which tively, for these three types, all of which that in men with an equal smoking his- were malignant) showed interval nodule were significantly different. In addition, tory, this has not been confirmed in growth detectable on 4 – 8-month fol- the mean volume doubling time for can- more recent studies (27–30). low-up scans. Therefore, they recom- cerous nodules in nonsmokers was signif- A history of lung cancer in first-degree mended that patients with nodules no icantly longer than that for cancerous relatives is also a notable risk factor, and larger than 5 mm in diameter on a base- nodules in smokers. The mean volume strong evidence for a specific lung cancer line screening CT scan should be referred doubling time was also significantly susceptibility gene has been discovered for repeat annual screening in 12 months longer for nodules not visible on chest recently (31,32). Other established risk time, with no interval scans. This recom- radiographs (presumably a function of factors include exposure to asbestos, ura- mendation differs only slightly from the their smaller average size and/or their nium, and radon (33–35). However, cig- current protocol for the ongoing Na- lesser average opacity). These data further arette smoke remains the overwhelm- tional Lung Screening Trial, in which pa- support the use of extended follow-up ingly dominant culprit. tients with nodules smaller than 4 mm in intervals for small nonsolid or partly Several large screening programs are diameter are recommended to return for solid nodules, even in high-risk patients. continuing, and we will learn more from screening after 12 months, without inter- Authors of a number of other series these studies in the next several years. val scans or other work-up. Note that (20,21) have confirmed similar findings Although the available data are still in- these recommendations refer to high-risk and have estimated the median tumor complete, certain tentative conclusions subjects who have enrolled in a screening doubling times, assuming a constant can be drawn at the present: program. growth rate to be in the 160 –180-day 1. Approximately half of all smokers A further practical issue arises in the range. Authors of all of these reports, over 50 years of age have at least one lung follow-up to detect interval growth of however, recognize wide variations, and nodule at the time of an initial screening very small nodules. Comparison of cur- in one study 22% of tumors had a vol- examination. In addition, approximately rent and previous scans can be performed ume doubling time of 465 days or more 10% of screening subjects develop a new by using hard copy with manual mea- (21). Note that a 5-mm nodule with a nodule during a 1-year period (36). surement, soft copy with electronic cali- doubling time of 60 days will reach a 2. The probability that a given nodule Volume 237 Number 2 Fleischner Society Statement on CT of Small Pulmonary Nodules 397
  • 4. is malignant increases according to its size (4,5). Even in smokers, the percent- Recommendations for Follow-up and Management of Nodules Smaller than 8 mm Detected Incidentally at Nonscreening CT age of all nodules smaller than 4 mm that will eventually turn into lethal cancers is Nodule Size very low ( 1%), whereas for those in the (mm)* Low-Risk Patient† High-Risk Patient‡ Radiology 8-mm range the percentage is approxi- 4 No follow-up needed § Follow-up CT at 12 mo; if mately 10%–20% (4,7,8,37). unchanged, no further follow-up 3. Cigarette smokers are at greater risk 4–6 Follow-up CT at 12 mo; if Initial follow-up CT at 6–12 mo then for lethal cancers, and malignant nodules unchanged, no further follow-up at 18–24 mo if no change 6–8 Initial follow-up CT at 6–12 mo then Initial follow-up CT at 3–6 mo then in smokers grow faster, on average, than at 18–24 mo if no change at 9–12 and 24 mo if no change do those in nonsmokers (19,25,26). Also, 8 Follow-up CT at around 3, 9, and 24 Same as for low-risk patient the cancer risk for smokers increases in mo, dynamic contrast-enhanced proportion to the degree and duration of CT, PET, and/or biopsy exposure to cigarette smoke (38). Note.—Newly detected indeterminate nodule in persons 35 years of age or older. 4. Certain features of nodules correlate * Average of length and width. † Minimal or absent history of smoking and of other known risk factors. with likelihood of malignancy, cell type, ‡ History of smoking or of other known risk factors. and growth rate. For instance, small § The risk of malignancy in this category ( 1%) is substantially less than that in a baseline CT scan purely ground-glass opacity (nonsolid) of an asymptomatic smoker. nodules that have malignant histopatho- Nonsolid (ground-glass) or partly solid nodules may require longer follow-up to exclude logic features tend to grow very slowly, indolent adenocarcinoma. with a mean volume doubling time on the order of 2 years (19). Solid cancers, on the other hand, tend to grow more rap- idly, with a mean volume doubling time be subjected to a minimum of four or five this regard. Rather, we have elected to on the order of 6 months. The growth follow-up CT examinations before being focus on the issue of follow-up imaging rate of partly solid nodules tends to fall designated benign and the patient being of smaller nodules. Specifically, for what between these extremes, and this partic- reassured (1,2). As summarized above, kinds of lesions is it appropriate to fol- ular morphologic pattern is highly pre- data from ongoing CT screening pro- low, and if followed, at what intervals? dictive of adenocarcinoma (39 – 41). grams with multidetector CT with 5-mm Therefore, we propose a set of guidelines, 5. Increasing patient age generally cor- collimation indicate that approximately summarized in the Table, for the man- relates with increasing likelihood of ma- half of all smokers over 50 years of age agement of small pulmonary nodules de- lignancy. Lung cancer is uncommon in have at least one lung nodule on the ini- tected on CT scans. patients younger than 40 years and is rare tial scan (36). In addition, approximately Note that the recommendations in those younger than 35 years (42). At 10% of screening subjects develop a new shown in the Table apply only to adult the other end of the age scale, although nodule over a 1-year period, and about patients with nodules that are “inciden- the likelihood of cancer increases, surgi- 12% can be expected to have one or more tal” in the sense that they are unrelated cal intervention carries greater risks. Also, additional nodules that were missed on to known underlying disease. The follow- the likelihood of a small nodule evolving the original scan (36). Assuming similar ing examples describe patients to whom into a cancer that will cause premature demographics, approximately 20% of pa- the above guidelines would not apply. death becomes a lesser concern as comor- tients who have a nodule detected on CT Patients known to have or suspected of bidity increases in a person and predicted scans can be expected to have at least one having malignant disease.—Patients with a survival decreases with advancing years. new nodule detected during the cur- cancer that may be a cause of lung me- rently recommended 2-year minimum tastases should be cared for according to follow-up period, which will in turn the relevant protocol or specific clinical Management Approach mandate another series of follow-up CT situation. Pertinent factors will include A number of investigators have already studies with similar opportunities for the site, cell type, and stage of the pri- raised serious concerns about current new nodules to be detected during the mary tumor and whether early detection management strategies for the indeter- additional follow-up period. Therefore, of lung metastases will affect care. In this minate small nodule, particularly after strict application of the existing recom- setting, frequent follow-up CT may be encountering an overwhelming number mendations would result in multiple fol- indicated. of such abnormalities on CT scans low-up studies over 2 or more years for a Young patients.—Primary lung cancer is (7,14,36). In the study by Henschke et al large proportion of all patients who un- rare in persons under 35 years of age (5) described earlier, the authors found dergo thoracic CT. ( 1% of all cases), and the risks from no cancers in patients in whom the larg- In the case of nodules larger than 8 radiation exposure are greater than in the est noncalcified nodule was less than 5 mm, additional options such as contrast older population. Therefore, unless there mm in diameter on the initial scan (zero material– enhanced CT, positron emis- is a known primary cancer, multiple fol- of 378 patients). Thus there was no ad- sion tomography (PET), percutaneous low-up CT studies for small incidentally vantage in performing short-interval fol- needle biopsy, and thoracoscopic resec- detected nodules should be avoided in low-up for nodules smaller than 5 mm in tion can be considered (43– 46). Because young patients. In such cases, a single their study, even in high-risk patients. these approaches depend greatly on low-dose follow-up CT scan in 6 –12 Therefore, we recommend altering the available expertise and equipment and months should be considered. existing recommendations, which indi- have limited applicability to nodules in Patients with unexplained fever.—In cer- cate that every indeterminate nodule, re- the subcentimeter range, we have chosen tain clinical settings, such as a patient gardless of size and morphology, should not to offer detailed recommendations in presenting with neutropenic fever, the 398 Radiology November 2005 MacMahon et al
  • 5. presence of a nodule may indicate active conclusive evidence, as yet, that serial CT malignancy and should be managed ac- infection, and short-term imaging fol- studies with early intervention for de- cordingly (39). Depending on the cir- low-up or intervention may be appropri- tected cancers can reduce disease-specific cumstances, follow-up imaging studies or ate. mortality, even in high-risk patients (7). intervention may be appropriate. Con- Previous CT scans, chest radiographs, Therefore, we do not recommend fol- servative management is generally ap- and other pertinent imaging studies low-up CT for every small indeterminate Radiology propriate for nodules in very elderly pa- should be obtained for comparison nodule. tients or in those with major comorbid whenever possible, as they may serve to Management decisions should not be disease. Interval growth of any nodule demonstrate either stability or interval based on nodule size alone. While any suggests an active process, and further growth of the nodule in question. calcification in a small nodule favors a evaluation or intervention should be A low-dose, thin-section, unenhanced benign cause, central, laminar, or dense considered in such cases. technique should be used, with limited diffuse patterns of calcification are reli- It is impossible to ignore medicolegal longitudinal coverage, when follow-up of able evidence of benignancy (49). Fat considerations when discussing manage- a lung nodule is the only indication for content suggests a hamartoma or occa- ment of pulmonary nodules. The current the CT examination. sionally a lipoid granuloma or lipoma practice in the United States of recom- (50). Solid versus nonsolid appearance, mending follow-up studies for all inde- spiculation, or other characteristics influ- terminate opacities is partly related to DISCUSSION ence the likelihood of malignancy and perceived liability if a cancer should de- probable growth rate in any given case velop (59). When the medical commu- Not every focal opacity qualifies as a nod- (19,39,49,51,52). Longer follow-up in- nity has preached the importance of ule. Unfortunately, the familiar lung tervals are appropriate for nonsolid early detection of cancer for so long, it nodule has eluded all efforts at precise (ground-glass opacity) and very small may prove difficult to convince physi- definition. A committee of the Fleischner opacities (19,40). For instance, even if cians and the public that follow-up CT of Society on CT nomenclature described malignant, a nonsolid nodule that is every nodule in every patient is unneces- the pathologic definition of a nodule as a smaller than 6 mm will probably not sary. Nonetheless, it is our hope that the “small, approximately spherical, circum- grow perceptibly in much less than 12 guidelines presented here will support a scribed focus of abnormal tissue” and the months (19,40). Also, as discussed earlier, practical and medically appropriate ap- radiologic definition as a “round opacity, it has been established that accurate mea- proach to the management of inciden- at least moderately well marginated and surement of growth in subcentimeter tally detected small pulmonary nodules. no greater than 3 cm in maximum diam- nodules is problematic (16). The recommendations presented here eter” (47). Therefore, a linear or essen- Other features such as clustering of are based on our current understanding tially two-dimensional opacity that does multiple nodules in a single location in of pulmonary nodules, and we expect not have an approximately spherical the lung tend to favor an infectious pro- that they will continue to evolve as more component is not a nodule. In general, cess, although a dominant nodule with information becomes available. purely linear or sheetlike lung opacities adjacent small satellite nodules can be are unlikely to represent neoplasms and seen in primary lung cancer (53,54). For a do not require follow-up, even when the single nodule, upper lobe location in- References maximum dimension exceeds 8 mm creases the likelihood of malignancy, be- 1. Ost D, Fein AM, Feinsilver SH. The solitary (48). cause primary lung cancers are more pulmonary nodule. N Engl J Med 2003; 348:2535–2542. Depending on their appearance and ra- common in the upper lobes (55). 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A history of can- 1997;157:849 – 855. 4. Midthun DE, Swensen SJ, Jett JR, Hartman case; in selected cases with suspicious cer can greatly increase the likelihood of TE. Evaluation of nodules detected by morphology or in high-risk subjects, a a nodule being malignant, depending on screening for lung cancer with low dose single follow-up scan in 12 months the nature and stage of the primary neo- spiral computed tomography. Lung Can- should be considered. We accept that this plasm (57). cer 2003;41(suppl 2):S40. 5. Henschke CI, Yankelevitz DF, Naidich DP, protocol could result in a few indolent The patient’s age and the presence of et al. CT screening for lung cancer: suspi- cancers being missed, but we believe that comorbid conditions should influence ciousness of nodules according to size on the number of such instances would be management recommendations (58). For baseline scans. 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