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Thoracic Imaging |
1 From the Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Founders House 2-202B, Boston, MA 02114. From the 1999 RSNA scientific assembly. Received March 5, 2001; revision requested April 8; final revision received June 14, 2002; accepted June 27. Address correspondence to M.S.B. (e-mail: matthew.benjamin@uhn.on.ca).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Reports of chest CT performed during 6 months were reviewed to find patients with pulmonary nodules smaller than 1 cm in long axis for which repeat CT was recommended. Records were studied to determine whether follow-up had been performed, the initial nodules had changed in size, or nodules had been resected.
RESULTS: A total of 3,446 chest CT examinations were performed, with 334 patients meeting inclusion criteria. Three patients underwent nodule resection and had pathologic examination results positive for cancer; 185 underwent follow-up, of whom 13 had results excluded as indeterminate. In the remaining 172 patients, 88 had incomplete characterization because of follow-up of less than 2 years, which left 84 with nodule characterization at follow-up. When these 84 patients were combined with the three patients with nodule resection, the number yielded was 87 patients. Seventy-seven of 87 had benign nodules because of resolution or 2-year stability, and 10 of 87 had malignant nodules because of growth or positive histologic examination results. Nine of 10 with malignant nodules had a known primary neoplasm.
CONCLUSION: CT commonly helped identify small nodules. Increase in size occurred infrequently and almost exclusively in patients with a known malignancy.
© RSNA, 2003
Index terms: Lung, CT, 60.12115 • Lung, nodule, 60.332, 60.333 • Lung neoplasms, 60.32, 60.33
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Helical computed tomography (CT) and its capacity for volumetric imaging during a single breath hold and thinner collimation have increased the number of nodules reliably detected (2). Helical CT has been shown to depict more nodules less than 1 cm than does conventional CT (3).
Currently, small nodules are managed in our department with helical CT follow-up. We consider nodules benign if they resolve, decrease in size, or demonstrate no perceptible growth for 2 years. Nodule growth is considered highly suggestive of malignancy. CT follow-up is recommended at 3-, 6-, and 12-month intervals. To our knowledge, no formal guidelines are in place for the characterization of small nodules. Some authors (1) have questioned whether 2-year stability is a reliable indicator of benignity. We performed this retrospective review to determine the outcome of pulmonary nodules less than 1 cm in diameter detected at chest CT.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Patient Selection
Our study received institutional review board approval. Informed consent was not required. We searched with keywords in the reports of all patients undergoing chest CT from July 1 through December 31, 1996, at our institution. These were the first 6 months during which all CT was performed with helical scanners. Using separate searches with the words "follow" and "nodule," we reviewed reports to determine those patients for whom follow-up examinations were recommended for pulmonary nodules less than 1 cm in maximum dimension. These words were selected to find the greatest number of patients meeting study inclusion criteria. "Follow" and "nodule" are the typical words used by radiologists in our department when recommending follow-up for small pulmonary nodules. Searches were performed with both words to find reports with atypical wording, such as "Follow-up is recommended to assess this 3-mm opacity," or "Repeat examination is recommended for the 3-mm nodule."
Our search included results of all chest CT. Indications ranged from staging for metastatic disease to aortic dissection. For this reason, many of the nodules were incidental findings.
Since calcified nodules are considered benign and do not require follow-up, the group of patients in our study did not include those with calcified nodules. Many patients had more than one nodule. No distinction was made between those with solitary nodules versus those with multiple nodules. Rather, all patients were included in the cohort in our study.
Patients were excluded if they were less than 18 years of age, had undergone pulmonary transplantation, or had an additional pulmonary nodule or mass greater than or equal to 1 cm in maximum dimension. If nodules were described in a report as small without explicit measurement, we reviewed the examination results on hard copy or an electronic workstation (AGFA Diagnostic Software, version 3.5; Agfa, Ridgefield Park, NJ) and measured the described nodules with calipers or the measuring tool.
Record Review
The records of the patients who met study inclusion criteria were reviewed by two of us (M.S.B., E.A.D.) to determine which patients underwent follow-up CT because of the nodules, which patients had a history of malignancy, and which patients underwent resection of the nodules and had results of pathologic analysis suggestive of disease. For patients who underwent follow-up CT, examination reports were reviewed to determine whether the initially described nodule or nodules had resolved, decreased in size, remained stable, or increased in size. A history of malignancy was sought from the clinical history accompanying the requests for CT and from any available discharge summaries from the last 5 years. Patients for whom no history of malignancy was described in a recent discharge summary were considered to have no primary malignancy. One of us (M.S.B.) reviewed these records. For some patients, there was no recent discharge summary or history of malignancy supplied on the CT requisition. These patients were classified in the category "unknown status" regarding the presence of primary neoplasm.
Records were reviewed in 1999 to allow a 2-year follow-up for the nodules. A group of the patients examined from July 1 through December 31, 1996, were already being followed up for nodules detected before July 1, 1996. In this setting, the length of follow-up was measured from the initial date of detection.
Image Analysis
Typically, radiologists in our department measured nodules along the long axis on the hard copy by using a caliper. A picture archiving and communication system was online in our department in the middle of 1998, and, thus, some follow-up examination results were reviewed on workstations. If the follow-up CT report did not address the initially described nodule, then the two physicians who performed the record review also reviewed the CT studies in consensus on hard copy or at the electronic viewing station to determine size changes in the nodules. These nodules were measured along the long axis by using handheld calipers or electronic calipers at the workstation. Cases in which the nodules could not be evaluated on follow-up scans were classified as indeterminate and were excluded.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Three (0.9%) of 334 patients underwent nodule resection and thus required no further examination for evaluation of their nodules. Pathologic examination results were positive for malignancy in four nodules in the three patients. Two of the resected nodules were 3 mm in long axis, and two were 5–9 mm in long axis.
One hundred eighty-five (55.4%) of 334 patients underwent follow-up CT at our hospital. Results in 13 of the 185 were excluded as indeterminate because the nodules were obscured by pleural fluid or consolidation or because hard copies of the CT images were unavailable for review; therefore, 172 patients underwent follow-up CT.
Fifty (29.1%) of 172 patients underwent final follow-up CT more than 2 years after the initial study. Nodules in these patients either remained stable or decreased in size during the 2 years. Thirty-six (20.9%) of 172 patients underwent final CT follow-up 1–2 years after the initial study. Fifty-nine (34.3%) of 172 patients underwent final follow-up CT less than 1 year after the initial study. Thus, 95 patients had less than 2-year follow-up. In 27 (15.7%) of 172 patients, the nodules resolved at follow-up examinations during the 2 years. Summing the number of patients with nodule resolution and the number of patients with 2-year stability produces 77 patients with benign nodules.
During the follow-up, seven (4.1%) of 172 patients demonstrated nodule growth. A typical example is presented in Figure 1. This growth was detected at the first follow-up scanning in all cases and occurred within 6 months in five cases and between 7 and 12 months in two cases. In these patients, the median and mean intervals between initial nodule detection and follow-up scanning were 5 months and 6.4 months, respectively. Two of the patients had nodules 1–3 mm in initial long axis, and five of the patients had nodules 4–8 mm in long axis.
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A sum of the number of patients with nodule growth (n = 7) and those with nodule resection and positive histologic examination results (n = 3) yields 10 patients with malignant nodules. If one combines the patients with malignant nodules and those with benign nodules, the total is 87 patients. In the 334 patients who met study inclusion criteria, only these 87 patients reached an end point because the other patients had indeterminate study results (n = 13), no follow-up (n = 146), or insufficient follow-up (n = 88) to confirm benignity. Thus, 77 (89%) of 87 patients had benign nodules. Ten (11%) of 87 patients had malignant nodules—seven were determined by means of nodule growth and three were determined by means of nodule resection with positive histologic examination results.
Nine of the patients with malignant nodules had a known primary malignancy. The 10th patient had no known malignancy at the time of the initial study, but pancreatic cancer was diagnosed during follow-up. This patient’s nodules were presumably malignant, as the nodules grew over time. However, tissue diagnosis was never performed.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Despite the widely varying rates, it is clear that small nodules are a common clinical problem. The current practice in our department and others is to confirm stability for 2 years by using follow-up CT. Some investigators (1) suggest that even longer periods are necessary to confirm benignity. Because of the high frequency with which small pulmonary nodules are detected at helical CT, the number of resultant follow-up scans is a substantial source of patient anxiety, radiation exposure, and medical cost.
Thus, investigators (7,8) have attempted to find means to characterize nodules according to such qualities as their enhancement and margins. Although these techniques appear promising, currently the only accepted clinical means of characterizing small nodules is follow-up.
In our series, growth of small pulmonary nodules was uncommonly observed in patients undergoing CT follow-up. Among the 87 patients who reached an end point in our study, 77 (89%) had nodules that were characterized as benign because of nodule resolution or documented 2-year stability. In contrast, 10 (11%) patients had nodules that were characterized as malignant because of either nodule resection or nodule growth.
Although our study results showed malignancy in 11% (10 of 87) who reached an end point, the rate may have actually been substantially lower. Forty-four percent (146 of 334) of the patients underwent no follow-up examination, and, thus, their nodules remain uncharacterized. Reasons for patients failing to undergo follow-up scanning were not specifically addressed but can be attributed to at least three factors: Referring physicians disregarded our recommendations regarding nodule follow-up. Patients underwent follow-up at outside institutions. Patients were noncompliant.
The malignancy rate in small nodules is a subject of debate and confusion within the literature. Authors of some studies claim rates as high as 58% (9), while others have found malignancy rates less than 10% (5). A closer review of the literature illustrates reasons for such discrepancies. Two types of studies exist that result in two different malignancy rates in small nodules (4,5,9–11). The first group of studies, including our own, relies on follow-up to distinguish benign from malignant nodules. For example, Keogan et al (4) investigated small 4–12-mm pulmonary nodules in patients with a known primary pulmonary cancer. The malignancy rate was 12%. Chalmers and Best (10) found a malignancy rate of 13% in patients with extrathoracic malignancies. These studies were limited by their population size (<25 patients). There were 145 patients with nodules 1 cm or smaller in the ELCAP study (5), and the malignancy rate was 8%.
Authors of the second group of studies evaluated results in patients who underwent surgery. Ginsberg et al (11) reviewed the records of 426 patients undergoing video-assisted thoracoscopic surgery for evaluation of nodules 3 cm or smaller in diameter. In this group of patients, 48% of nodules 1 cm or smaller in diameter were malignant. It should be noted that the data described a malignancy rate in resected nodules and not in patients. Thus, the malignancy rate per patient may have been lower. Munden et al (9) performed a similar study. This group evaluated nodules 1 cm or smaller in diameter that were resected at video-assisted thoracoscopic surgery, and the malignancy rate was 58%. In contrast to the study by Ginsberg et al (11), in the study by Munden et al (9), only one patient had more than one nodule, which allows for an approximation of the malignancy rate per nodule and per patient.
Why should the malignancy rates in these studies vary by such a large degree? The studies relying on follow-up may lead to underestimation of the malignancy rate. In our study, we characterized nodules according to their change in size over time, with pathologic proof of malignancy in three patients. Malignant nodules can resolve or decrease in size after therapy or grow so slowly that they appear unchanged at subsequent examinations.
On the other hand, in the studies with pathologic proof the malignancy rate is likely overestimated by an even greater degree (6,9,11). Clearly, only patients with nodules with suggestive imaging characteristics undergo surgery for characterization, and, thus, studies with pathologic proof have marked selection bias. Hazelrigg et al (6) performed a study with pathologic proof but with limited selection bias. Their evaluation included nodules detected at CT and at surgery in patients who underwent pulmonary reduction surgery. In that study, the malignancy rate was 21.8% per nodule (143 nodules were found in 111 patients). Yet, even in this population there is still substantial selection bias, since most patients who undergo pulmonary reduction surgery are prior smokers with severe emphysema.
Additional bias is related to the percentage of patients with known primary malignancies included in a study. Patients with known primary malignancies should theoretically have a higher malignancy rate in small pulmonary nodules than do patients without known primary malignancies. In our study, which included almost all patients who underwent chest CT, nine (90%) of 10 patients whose nodules were characterized as malignant, by means of either interval growth or nodule resection, had a known primary neoplasm. One patient had no known primary neoplasm at the time of the initial study. Pancreatic adenocarcinoma was diagnosed in this patient during the 2-year follow-up. In contrast to this rate of 90%, 56% of the patients who met study inclusion criteria had a known primary neoplasm. These findings suggest that the nodules of patients with primary neoplasms have a greater risk of malignancy.
The patient populations of Ginsberg et al (11) and Munden et al (9) had rates of known primary cancers of 74% and 42%, respectively. The pulmonary cancer screening trial, ELCAP, does not include patients with known primary malignancies and has a much lower malignancy rate of small pulmonary nodules (5). These data support our hypothesis that patients without a known primary cancer have a lower malignancy rate in small pulmonary nodules.
In regard to the proper management of small pulmonary nodules, our data suggest that short-interval follow-up is helpful. Nodule growth was found at the first follow-up examination in all cases. The interval between the initial examination and the first follow-up CT was 3–11 months, with a median of 5 months. A typical example is presented in Figure 2. The use of short-interval follow-up is also supported by the observations of Keogan et al (4). Of the three patients with nodule growth in their study, two had growth detected at CT 2 months after the initial examination. Finally, Yankelevitz et al (12) experimentally and clinically demonstrated that for nodules greater than 5 mm CT can depict malignant nodule growth within 30 days. Thus, data suggest that short-interval follow-up at 3 months is important for timely diagnosis.
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In summary, according to the data in this study, small nodules detected at CT are a common clinical problem and are more likely to be malignant in patients with known primary neoplasms, and a short-interval follow-up at 3 months can be of benefit for a timely diagnosis. It is clear that patients who have a known primary neoplasm or are at increased risk for pulmonary cancer deserve careful follow-up. Our study results suggest that the malignancy rate in small pulmonary nodules in patients without a known primary neoplasm may be as low as 1%. Follow-up examinations may not be necessary in this group of patients. Prospective studies are warranted to evaluate this issue further.
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, M.S.B.; study concepts and design, M.S.B., E.A.D.; literature research, M.S.B., E.A.D.; clinical studies, M.S.B., E.A.D.; data acquisition, M.S.B.; data analysis/interpretation, M.S.B., E.A.D.; statistical analysis, M.S.B., E.A.D.; manuscript preparation, definition of intellectual content, editing, revision/review, and final version approval, all authors.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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