eISSN: 1897-4252
ISSN: 1731-5530
Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Reviewers Abstracting and indexing Contact Instructions for authors Publication charge Ethical standards and procedures
Editorial System
Submit your Manuscript
SCImago Journal & Country Rank
1/2018
vol. 15
 
Share:
Share:
Original paper

Diagnostic value of 18F-FDG-PET/CT in benign lung diseases

Ayse Gul Ergonul
,
Tevfik Ilker Akcam
,
Ali Özdil
,
Kutsal Turhan
,
Alpaslan Cakan
,
Ufuk Cagirici

Kardiochirugia i Torakochirurgia Polska 2018; 15 (1): 1-4
Online publish date: 2018/03/28
Article file
- Diagnostic value.pdf  [0.19 MB]
Get citation
 
PlumX metrics:
 

Introduction

Positron emission tomography (PET) is a nuclear medical method which has been increasingly used in the assessment and definition of thoracic diseases using advanced computerized camera systems in combination with several radiopharmaceuticals [1]. The most commonly used radiopharmaceutical is 18F fluoro-2-deoxyglucose (FDG) in PET scanning. It is currently a widely used method for metabolic imaging, particularly in the distinction of solitary pulmonary nodules as being benign or malignant, in the staging of non-small cell lung cancer, in the assessment of treatment responses, in the exact localization of the tumor focus, in the detection of recurrent diseases to protect the surrounding tissue, and to increase the effectiveness of treatment in patients undergoing radiotherapy.
One of the major indications of 18F-FDG-positron emission tomography (PET)/computed tomography (CT) is the detection of solitary pulmonary nodules (SPN). The accumulation of 18F-FDG indicates malignancy. The semi-quantitative analysis that is performed using the standardized uptake value (SUV) together with a visual assessment increases the accuracy of diagnosis. The mean threshold value of SUV to differentiate benign and malignant lesions is 2.5. The sensitivity of the method is between 88% and 96% and its specificity is between 78% and 92% [2–4]. The size of the lesion is also important in the assessment of pulmonary lesions with 18F-FDG-PET. False-negative results may be yielded in lesions smaller than 1 cm, as metabolically active malignant cells should be at a certain mass for the visualization of the lesion with PET. False-negative 18F-FDG-PET uptake is observed in tumors with low metabolism, such as lepidic dominant adenocarcinoma and carcinoid tumors, and its sensitivity in these tumors is below 50%. On the other hand, false-negative 18F-FDG-PET uptake can be seen in diseases demonstrating granulocyte and/or macrophage activity, such as pneumonia, tuberculosis, sarcoidosis, and Wegener’s granulomatosis, and following a surgical procedure [3, 5, 6].

Aim

In the present study, we aimed to evaluate the PET results of patients who underwent resection with a preliminary diagnosis of malignancy according to the FDG uptake value, but diagnosed as benign pathologically.

Material and methods

A total of 862 patients who had an initial diagnosis of malignancy due to the presence of several lesions on the lungs and who underwent PET/CT and were surgically treated between January 2012 and December 2015 were retrospectively analyzed (Fig. 1). Of these, 106 patients who were operated on with an initial diagnosis of malignancy and whose pathology results were reported as benign were included. Diagnoses, PET findings, type of surgery, and demographic data of the patients were recorded.
The study protocol was approved by the local Ethics Committee. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Statistical analysis

Statistical analysis was performed using the SPSS v22.0 (IBM Corporation, Armonk, New York, United States) software. The conformity of data to a normal distribution was evaluated with the Shapiro-Wilk test and variability coefficient and variance homogeneity were evaluated with the Brown-Forsythe test. While the independent samples t-test was used together with the bootstrap results to compare the two independent groups, the Mann-Whitney U-test was used with the Monte Carlo simulation technique. Among the parametric methods, one-way analysis of variance (ANOVA) was used to compare independent multiple groups. Among the non-parametric tests, the Kruskal-Wallis H-test was used together with the Monte Carlo simulation test for the post-hoc analysis (non-parametric post-hoc test (Miller (1966)). Kendall’s tau-b test was used to investigate the correlation between the variables. The relationship between the true classification and the classification according to the calculated cut-off value of variables was expressed in sensitivity and specificity values using a receiver operating characteristics (ROC) curve. The quantitative data were expressed as the mean ± standard deviation (SD) and median and range (min.–max.). Categorical data were expressed as numbers (n) and percentages (%). A p-value of < 0.05 was considered statistically significant with a confidence level of 95%.

Results

Out of 106 patients included in the study, 46 (43.4%) were female and 60 (56.6%) were male. The mean age was 55.5 ±11.95 (range: 26–79) years. The mean diameter of lesions was 2 ±2.14 (range: 0.5–13) cm and the mean SUVmax value was 3.55 ±4.35 (range: 0–22.2). The pathological diagnosis was granulomatous diseases (sarcoidosis or tuberculosis) in 31 (29.2%) patients, hamartoma in 19 (17.9%) patients, interstitial lung disease in 18 (17%) patients, intraparenchymal reactive lymph node in 12 (11.3%) patients, and diagnoses that were grouped as “other”, such as typical carcinoid, hyalinizing nodule, hemangioma, and abscess, in the remaining 26 (24.5%) patients (Table I). A wedge resection was performed on 75 (70.8%) patients, biopsy was performed on 22 (20.8%) patients, and lobectomy was performed on 9 (8.5%) patients. Among all groups, the SUVmax value was lower in the patients with hamartomas, compared to the other groups (p < 0.001). However, the SUVmax value was higher in the patients with granulomatous diseases compared to other groups (p < 0.001) (Fig. 2). The diameter of the lesion also increased as the SUVmax value increased (p < 0.001). On the other hand, we found no significant correlation between the SUVmax values and variables such as age, sex, and comorbidities.

Discussion

Globally, PET has become one of the main imaging techniques to examine and visualize several biological events, as it provides physiological data which cannot be obtained by anatomical imaging methods thanks to its more sophisticated sensitivity and better resolution rates compared to other nuclear imaging modalities. It is the most accurate imaging method for the evaluation of suspicious pulmonary lesions visualized in radiography or tomography, and also in the distinction and definition of benign or malignant lesions [7]. The accumulation of 18F-FDG in the visualized lesion supports the diagnosis of malignancy. It is accepted that the possibility of malignancy has increased in lesions with SUV values greater than 2.5 [3]. These lesions are diagnosed using diagnostic procedures such as bronchoscopy and biopsy. If there is clinical suspicion and if the diagnosis is not possible, surgical diagnostic methods are used. However, upon consideration of the possibility of false positivity, as mentioned in the current study, frozen section examination should be performed during the surgery before deciding on resection. Recent studies have shown new calculation methods developed to decrease the incorrect assessment of PET/CT and the relative activity distribution (RAD) method, which could be more effective in the distinction of malignant and benign lesions [8]. In the current study, the mean SUV value of granulomatous lung diseases was calculated as 5.9 and there were lesions with a maximum SUV value of 15.8. Although these values had high suspicion of malignancy, when frozen section examination was performed and the patient was diagnosed with granulomatous disease, the surgical procedure was terminated without extension. False negative 18F-FDG uptake is observed in tumors with low metabolism such as lepidic dominant adenocarcinoma or carcinoid tumors. As only benign lesions were included in the current study, false negativity was not evaluated. However, the hamartoma SUV value was found to be between 0 and 4.5 and, compared to all other lesions, it was significantly low. Although a lobectomy was conducted on large lesions which were found to be hamartomas during the operation, limited surgery was done to the lesions that could be removed by small resections.
In a meta-analysis evaluating the publications related to PET in solitary pulmonary nodules, the sensitivity of 18F-FDG-PET was 96.8% and its specificity was 77.8%; the negative predictive value was 97.6% in nodules greater than 1 cm. According to this result, the probability of cancer is lower than 3% in nodules greater than 1 cm which do not demonstrate 18F-FDG uptake [9]. Similar to the study of Yilmaz et al. [10], when the diameter of the lesion and SUV values were compared in the current study, as the diameter increased, the SUV value also significantly increased.
Using radionucleotide amino acid transferring agents such as 11C-L-methionine and 18F-fluoro-alpha-methyl-tyrosine, which are more specific to cancer, instead of using 18F-FDG, has led to more promising results [11–13].

Conclusions

Our study results suggest that PET, which currently has widespread use, may give false-positive results in lesions with high SUV values, particularly in countries where granulomatous diseases are frequently encountered, such as Turkey, and it is necessary to perform more exact preoperative evaluation and to make the decision for resection after performing frozen section examination during surgery.

Disclosure

Authors report no conflict of interest.

References

1. Cherry CR, Phelps ME. Positron emission tomography: methods and instrumentation. In: Diagnostic Nuclear Medicine. Sandler MP (ed.) Fourth edition. Lippincott Williams-Wilkins, Philadelphia 2003; 61-83.
2. Rohren EM, Lowe VJ. Update in PET imaging of non-small cell lung cancer. Semin Nucl Med 2004; 34: 134-153.
3. Bunyaviroch T, Coleman RE. PET evaluation of lung cancer. J Nucl Med 2006; 47: 451-469.
4. Grgic A, Yüksel Y, Gröschel A, Schäfers HJ, Sybrecht GW, Kirsch CM, Hellwig D. Risk stratification of solitary pulmonary nodules by means of PET using 18F-flourodeoxyglucose and SUV quantification. Eur J Nucl Med Mol Imaging 2010; 37: 1087-1094.
5. Schrevens L, Lorent N, Dooms C, Vansteenkiste J. The role of PET scan in diagnosis, staging and management of non-small cell lung cancer. Oncologist 2004; 9: 633-643.
6. Behzadi A, Ung Y, Lowe V, Deschamps C. The role of positron emission tomography in the management of non-small cell lung cancer. Can J Surg 2009; 52: 235-242.
7. Aras G. Evaluation of thorax by radyonuclid methods. Cilt, İstanbul Tıp Kitabevi, 2013; 167-188.
8. Zhao L, Tong L, Lin J, Tang K, Zheng S, Li W, Cheng D, Yin WW, Zheng XW. Characterization of solitary pulmonary nodules with 18F-FDG PET/CT relative activity distribution analysis. Eur Radiol 2015; 25: 1837-1844.
9. Gould MK, Sanders GD, Barnett PG, Rydzak CE, Maclean CC, McClellan MB, Owens DK. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003; 138: 724-735.
10. Yilmaz F, Tastekin G. Sensitivity of 18F-FDG PET in evaluation of solitary pulmonary nodules. Int J Clin Exp Med 2015; 8: 45-51.
11. Grierson JR, Shields AF. Radiosynthesis of 3’-deoxy-3’-[(18)F] flourothymidine: [(18)F] FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 2000; 27: 143-156.
12. Han D, Yu J, Zhong X, Fu Z, Mu D, Zhang B, Xu G, Yang W, Zhao S. Comparison of the diagnostic value of 3-deoxy-3-18F-flourothymidine and
18F-flourodeoxyglucosepositron emission tomography/computed tomography in the assessment of regional lymph node in thoracic esophageal squamous cell carcinoma: a pilot study. Dis Esophagus 2012; 25: 416-426.
13. Morita M, Higuchi T, Achmad A, Tokue A, Arisaka Y, Tsushima Y. Complementary roles of tumour specific PET tracer 18F-FAMT to 18F-FDG PET/CT for the assessment of bone metastasis. Eur J Nucl Med Mol Imaging 2013; 40: 1672-1681.
Copyright: © 2018 Polish Society of Cardiothoracic Surgeons (Polskie Towarzystwo KardioTorakochirurgów) and the editors of the Polish Journal of Cardio-Thoracic Surgery (Kardiochirurgia i Torakochirurgia Polska). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2024 Termedia Sp. z o.o.
Developed by Bentus.