Japanese Journal of Clinical Oncology 31:51-54 (2001)
© 2001 Foundation for Promotion of Cancer Research
Differentiation of Radiographically Indeterminate Solitary Pulmonary Nodules with [18F]Fluoro-2-deoxyglucose Positron Emission Tomography
1Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, 2Department of Nuclear Medicine, Far Eastern Memorial Hospital and Institute of Biomedical Engineering, College of Electrical Engineering, National Taiwan University, Taipei, 3Department of Nuclear Medicine, Show-Chwan Memorial Hospital, Chunghua, 4Department of Radiology, Jen-Ai Hospital, Taichung and 5Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: The purpose of this preliminary study was to evaluate the efficacy of positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (FDG) for differentiating benign from malignant solitary pulmonary nodules.
Methods: Twenty-six patients (12 females, 14 males, age 27–79 years) with radiographically indeterminate solitary pulmonary nodules underwent FDG-PET and the findings were compared with the results of pathological examination of biopsy samples. FDG activity in the lesion was expressed as the ratio of lesion-to-background counts (L/B ratio) for semiquantitative analysis.
Results: The mean L/B ratio of malignant lesions (8.81 3.71, n = 20) was not significantly higher than that of benign lesions (4.71 3.00, n = 6) (p = 1.00). Using a cut-off L/B ratio of 5.0 for malignancy, FDG-PET correctly detected 19 true positive and three true negative cases, but failed to detect three false positive (two abscesses and one cryptococcus) cases and one false negative (adenocarcinoma) case. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 95, 50, 86, 75 and 85%, respectively.
Conclusions: FDG-PET is a sensitive modality for detecting malignancy, but is not specific enough. Benign lung lesion with active inflammation could demonstrate high FDG uptake, making it difficult to differentiate from malignancy. In the future, we will increase the case numbers to evaluate further the utility of FDG-PET for differentiating radiographically indeterminate solitary pulmonary nodules.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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It is always a diagnostic challenge to differentiate malignant and benign solitary pulmonary nodules. Conventional imaging modalities including chest radiograph, computed tomography (CT) and magnetic resonance imaging (MRI) provide anatomical and morphological information. However, with these modalities many lesions remain indeterminate in nature (1) and histologic biopsies are often required to establish definite diagnoses. Because of the morbidity and high cost of invasive procedures, imaging techniques that demonstrate the metabolic properties of a lesion have attracted increasing interest, especially in differentiating benign from malignant solitary pulmonary nodules.
Positron emission tomography (PET), a non-invasive imaging modality using [18F]fluoro-2-deoxyglucose (FDG), has demonstrated higher glucose metabolism in malignant cells (2). Quantitative studies have documented a significantly higher metabolic rate in pulmonary carcinoma than in normal lung (3). Recent studies have also shown the utility of FDG-PET in the differential diagnosis of indeterminate solitary pulmonary nodules (4–6), in the staging of bronchial carcinoma (7) and in the detection of recurrent tumors (5,8). In the present study, we evaluated the usefulness of FDG-PET for distinguishing benign and malignant indeterminate solitary pulmonary nodules. Diagnostic biopsy was still needed in patients with positive FDG-PET.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Twenty-six patients (12 females, 14 males, age 27–79 years) with suspected lung cancer detected by chest radiograph and CT scan were referred for FDG-PET scan. Final diagnosis was established by pathological examinations in all patients. The findings of pathological examinations were compared with the results of FDG-PET imaging. The diagnostic efficacy of FDG-PET imaging in differentiating benign from malignant solitary pulmonary nodules was determined by calculating sensitivity, specificity and positive and negative predictive values.
All patients fasted for more than 4 h before the PET study, then 10 mCi (370 MBq) of FDG were administered intravenously 30 min before imaging. PET imaging was performed with a General Electric (Milwaukee, WI) Advance PET system and the images were processed and reconstructed with a Hewlett-Packard (Andover, MA) Apollo Series 735 system. No attenuation correction was performed. For calculating the lesion-to-background (L/B) ratio for semiquantitative analysis, the region of interest (ROI) for the lesion was drawn over the area of highest intensity of FDG activity, that corresponded to radiographic abnormalities (9). The background ROI was drawn over a homologous region of the lung contralateral to the lesion. A pulmonary lesion was defined as malignant when the L/B ratio was 
5.0, as previously described (10).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The results of FDG-PET imaging and pathological examinations are summarized in Table 1. Overall, 20 patients had malignant lesions (adenocarcinoma, 13; adenosquamous carcinoma, 2; squamous cell carcinoma, 2; bronchoalveolar carcinoma, 1; poorly differentiated carcinoma, 1; and carcinoid, 1) and six had benign lesions (abscess, 2; organizing pneumonia, 2; cryptococcus, 1; and non-specific inflammation, 1). The average L/B ratio was 8.81 ± 3.71 for malignant lesions and 4.71 ± 3.00 for benign lesions. There was no statistically significant difference between the L/B ratios of malignant and benign lesions (p = 1.00, Mann–Whitney U test). Using a cut-off L/B ratio of 5.0 for malignancy, FDG-PET correctly identified malignancy in 19 of 20 patients. A typical true positive lesion is shown in Fig. 1. The FDG uptake did not increase significantly in one patient with a 1.2 cm adenocarcinoma (L/B ratio = 3.32). Of the six patients with benign lesions, there were three false positive cases including two with abscess (L/B ratio 7.8 and 6.0) and one with cryptococcus (L/B ratio 8). Fig. 2 shows a typical false positive case. The sensitivity and specificity for detecting malignancy in indeterminate focal pulmonary abnormalities were 95 and 50%, with positive predictive value of 85% and negative predictive value of 75%. The overall diagnostic accuracy was 86%.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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FDG-PET images demonstrate the metabolic differences in benign and malignant tissues and can be analyzed in several different ways, including qualification by visual comparison of the abnormality with normal structures, semiquantification using standardized uptake ratios (SUR) or L/B ratios or absolute quantification of glycolysis. Lowe et al. (11) found that SUR, activity ratios and visual evaluation were equally accurate in differentiating malignant from benign pulmonary abnormalities. A study by Imuran et al. (9) showed similar diagnostic efficacies for attenuation-uncorrected and attenuation-corrected FDG-PET images. In addition, non-attenuation-corrected images obviate the need for transmission scans which consume extra time and might be an undue burden on machines and patients. However, the L/B ratio is the only available index for semiquantification of uncorrected images. We did not perform attenuation correction in the present study and used the L/B ratio for semiquantitative analysis to augment visual interpretation.
In recent reports (4–6,12–14), FDG-PET has been shown to be useful for characterizing solitary pulmonary nodules or focal pulmonary masses, that are indeterminate on chest radiograph and/or CT scan, as benign or malignant (Table 2). The sensitivity, specificity and accuracy of these studies ranged from 90 to 100%, from 67 to 89% and from 87 to 94%, respectively. Our results showed a similarly high sensitivity of 95% (19 of 20) with only one false negative case. Therefore, observation, rather than expensive and invasive procedures, is recommend for patients with negative FDG-PET.
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However, the specificity of FDG-PET in this study, 50%, was significantly lower than that in previous studies. Among the six benign lesions, there were three false positive cases, including two abscesses (L/B ratios 7.8 and 6) and one cryptococcus infection (L/B ratio 8). The L/B ratios of these three cases were even higher than those of some malignant cases. In addition, there was no statistical difference in the L/B ratios of benign and malignant lesions. This result might be partially the result of the selection bias of relatively fewer benign cases. High FDG uptake in inflammatory processes, especially granulomatous pulmonary diseases such as tuberculosis, makes it difficult to differentiate benign and malignant lesions. Previous studies have reported high FDG uptake in benign pulmonary abnormalities, including pneumonia, aspergillosis, histoplasmosis, cryptococcus, tuberculosis, lung abscess, Wegener granuloma, sarcoidosis, aggressive neurofibroma, inflammatory pseudotumor, Schwannoma and mesothelioma (10,11,15).
When the diagnostic accuracy was evaluated by separating the nodules into those between 0.7 and 1.5 cm in diameter and comparing them with those >1.5 cm in diameter, the sensitivity and the specificity were not statistically different (16). Data are not available concerning the accuracy of detecting nodules <0.7 cm in diameter. Because of scanner resolution and nodule motion during the acquisition, accurate detection of nodules <0.7 cm in diameter is unlikely. False-negative FDG-PET scans have been reported to occur with primary pulmonary carcinoid tumors and with bronchoalveolar cell cancers (17,18). Carcinoid tumors and bronchoalveolar cell cancers are slower growing and demonstrate milder mitotic activity, factors that might result in less FDG uptake than in other lung cancers. In addition, a correlation was found between the amount of FDG uptake and the degree of cell differentiation in adenocarcinoma of the lung (17,18).
In conclusion, our preliminary study demonstrated that FDG-PET is a sensitive modality for detecting malignancy, but is not specific enough. Benign lung lesions with active inflammation could demonstrate high FDG uptake, making it difficult to differentiate benign from malignant solitary pulmonary nodules. A solitary pulmonary nodule with increased FDG uptake still requires a biopsy for definite diagnosis. In the future, we will increase the case numbers to evaluate further the utility of FDG-PET in differentiating solitary pulmonary nodules.
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FOOTNOTES |
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+ For reprints and all correspondence: Chia-Hung Kao, Department of Nuclear Medicine, Taichung Veterans General Hospital, 160 Taichung Harbor Road, Section 3, Taichung 407, Taiwan. E-mail: kaoch@vghtc.vghtc.gov.tw
Abbreviations: PET, positron emission tomography; FDG, [18F]fluoro-2-deoxyglucose; L/B, lesion-to-background counts; CT, computed tomography; MRI, magnetic resonance imaging
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Received September 22, 2000; accepted November 17, 2000.
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