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HEAD AND NECK SYMPOSIUM - ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 3  |  Page : 236-240
 

Evaluation of focal thyroid lesions incidentally detected in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography images


Department of Nuclear Medicine, Pamukkale University Medical Faculty, Denizli, Turkey

Date of Web Publication10-Dec-2014

Correspondence Address:
O Yaylali
Department of Nuclear Medicine, Pamukkale University Medical Faculty, Denizli
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.146737

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 » Abstract 

Background and Purpose: Increased uptake in the thyroid gland (TG) is often identified as an incidental finding on the whole body fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in non-thyroid cancer patients. Currently, there is no consensus on the appropriate approach for the management of these cases. Thyroid ultrasound, scintigraphy and fine-needle aspiration biopsy (FNAB) are suggested to exclude malignant thyroid lesions. Our aim is to determine the importance of increased F-18-FDG uptake in the TG on positron emission tomography/computed tomography (PET/CT) scans in patients who are being screened for various forms of non-thyroid cancer. Materials and Methods: We evaluated 2000 cases undergoing whole body PET/CT scanning between April 2011 and October 2012. The age, sex, type of primary cancer, maximum standardized uptake value (SUV max ), size of the thyroid nodules and cervical lymph nodes (CLNs) on 18 F-FDG PET/CT images and if available, the biopsy results were evaluated. Results: In total, 57 patients (23 men, 34 women, mean age ± standard deviation (SD), 60.89 ± 14 years) showed an increased fluorine-18-fluorodeoxyglucose ( 18 F-FDG) uptake by the TG (average SUV max : 4.07 ± 3.7). The CLNs were detected in 19/57 patients (33%). Only 20 cases (35%) received FNAB. The final histopathological diagnosis was papillary thyroid carcinoma in seven patients (mean SUV max ± SD: 6.0 ± 5.43) and benign thyroid disease in seven patients (mean SUV max ± SD: 2.36 ± 0.63). The FNAB results were undetermined for six patients. Conclusion: Focal high 18 F-FDG uptake in the TG may be associated with an increased risk of malignancy, but the clinical significance is unclear. More data are needed to elucidate the role of the SUV in the differentiation of benign and malign thyroid lesions. If a focal increase in 18 F-FDG uptake in the TG on PET/CT is present, a prompt histopathological evaluation should be suggested to clinicians for definitive diagnosis.


Keywords: Fluorine-18-fluorodeoxyglucose, incidental uptake, positron emission tomography/computed tomography, thyroid nodule


How to cite this article:
Yaylali O, Kirac F S, Yuksel D, Marangoz E. Evaluation of focal thyroid lesions incidentally detected in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography images. Indian J Cancer 2014;51:236-40

How to cite this URL:
Yaylali O, Kirac F S, Yuksel D, Marangoz E. Evaluation of focal thyroid lesions incidentally detected in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography images. Indian J Cancer [serial online] 2014 [cited 2019 Sep 22];51:236-40. Available from: http://www.indianjcancer.com/text.asp?2014/51/3/236/146737



 » Introduction Top


Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) is increasingly performed for staging or localization of metastatic disease in patients with various kinds of malignancies that show increased glucose utilization compared with normal tissues. Focal or diffuse increased fluorine-18-fluorodeoxyglucose ( 18 F-FDG) uptake in the thyroid gland (TG) is often identified as an incidental finding on the whole body positron emission tomography/computed tomography (PET/CT) in non-thyroid cancer patients. [1],[2],[3],[4] With regard to thyroid nodules, there are many reports describing pre-operative evaluation with FDG-PET. It is generally believed that FDG-PET has only limited value for predicting thyroid cancer. [2],[3],[4],[5] The normal TG is usually not visualized on FDG-PET images. [5],[6] However, some results of previous PET studies have indicated that diffuse or focal fluorodeoxyglucose (FDG) uptake can also be seen in normal TGs. [7],[8]

Several retrospective studies have reported that thyroid incidentalomas with focal increased 18 F-FDG uptake were found in 1.2-4.3% of patients on PET examinations. The risk of malignancy was defined with a range from 14% to 50% in those studies. [1],[2],[3],[4],[5] Although there was a significant difference in the standardized uptake values (SUVs) between benign and malignant thyroid lesions, it is still difficult to differentiate benign from malignant thyroid incidentalomas by SUV alone. [1],[2],[3],[9],[10] The recently developed FDG-PET/CT provides a significant improvement in the diagnostic accuracy. [11],[12],[13] Currently, there is no consensus on the appropriate approach for the management of these cases. Thyroid ultrasound, scintigraphy and fine needle aspiration biopsy (FNAB) are suggested to exclude malignant thyroid lesions.

The purpose of this study was to investigate the prevalence of incidental thyroid FDG uptake and to determine the importance of increased 18 F-FDG uptake in the TG on PET/CT in patients who are being screened for various non-thyroid cancers.


 » Materials and Methods Top


We retrospectively evaluated 2000 cases undergoing whole body PET/CT scanning at our institute between April 2011 and October 2012. A focal thyroid lesion accumulating 18 F-FDG associated with a nodular appearance on a CT image was regarded as a focal thyroid lesion in the study. The age, sex, type of primary cancer, SUV max and the size of thyroid nodules and cervical lymph nodes (CLNs) on 18 F-FDG-PET/CT images and if available, FNAB results were evaluated in the present study. Incidental thyroid FDG uptake was defined as a newly identified thyroid lesion on the PET scan in our patient group without previously known thyroid disease.

18 F-FDG-PET/computed tomography

Written informed consent was obtained from all patients before enrollment. The study protocol confirms to the ethical guidelines Declaration of Helsinki (British Medical Journal, 1964, ii, 177). Ethics approval is not required for retrospective studies in our country according to The Regulations on Clinical Trials. Therefore, we did not get ethics approval for our retrospective study. All subjects fasted for at least 6 h before the PET study. The blood glucose levels were measured before the FDG injection and if the finger stick glucose levels were lower than 160 mg/dL, the patients received an intravenous injection of 3.7 MBq/kg 18 F-FDG. PET/CT scanning was performed 60 min after the injection of 18 F-FDG with the Gemini TF TOF PET/CT scanner (Philips Medical Systems, USA). Whole body CT was performed using a 16-slice helical CT. The CT scan data were collected at 50-120 mAs and 90-140 kV adjusted to the patient's body weight. No intravenous contrast material was used. After the CT scan, an emission scan was obtained from head to feet at a rate of 20 to 60 s per frame, 45-60 min after the intravenous injection of 18 F-FDG. Attenuation-corrected PET images using the CT data were reconstructed using an ordered subset expected maximization algorithm (33 subsets, 3 iterations). Commercial software (Extended Brilliance Workspace, Philips Medical Systems, USA) was used to accurately co-register the CT and PET scan data. The maximum SUV (SUV max ) were calculated using the attenuation-corrected images, the amount of injected 18 F-FDG, the body weight of each patient and the cross-calibration factors between the PET and the dose calibrator. The PET image, the non-contrast CT image and the fused PET/CT image were reviewed retrospectively by two nuclear medicine physicians who were unaware of the patient's clinical findings.

Statistical analysis

The statistical analysis was performed using the Statistical Packages for the Social Sciences 17 (SPSS 17, Inc., Chicago, IL, USA) software package. The prevalence was calculated as the percentage of prevalent focal incidental thyroid FDG uptake among the total study population. The numerical data were expressed as the mean ± standard deviation (SD). The data were expressed as the percentage of focal incidental thyroid FDG uptake among the population. The comparisons of SUV max and nodule size between the benign and malignant lesions of the focal thyroid FDG-PET incidentaloma were analyzed by the Student's t-test. A P < 0.05 was considered to be significant.


 » Results Top


Of the 2000 cases that we considered 57 had been detected as incidentally focal thyroid lesions (23 men, 34 women, mean age ± SD, 60.89 ± 14 years) on 18 F-FDG PET/CT scans, resulting in prevalence of focal uptake of 2.9%. 57 thyroid lesions in the 57 cases showed an increased focal 18 F-FDG uptake in the TG with a mean SUV max ± SD of 4.07 ± 3.7. The normal SUV max value for thyroid tissue was 1.30 ± 0.43. The thyroid lesions ranged in diameter from 5.0 to 55.0 mm (mean ± SD: 16.23 ± 10.11 mm). CLNs were detected in 19/57 patients (33%). Only 20 cases out of the 57 with focal uptake (35%) underwent FNAB. The final histopathological diagnosis was papillary thyroid carcinoma [Figure 1] in seven patients (35%) (mean SUV max ± SD: 6.0 ± 5.43) and benign thyroid disease [Figure 2] was reported in seven patients (mean SUV max ± SD: 2.36 ± 0.63). The FNAB results were undetermined for six patients (mean SUV max ± SD: 3.54 ± 0.87). Further evaluation was not performed on these six patients with undetermined results and the remaining 37 cases (37/57) did not have an FNAB result as they refused any additional work-up, they were lost to clinical follow-up, or they had an extensive underlying primary malignancy.
Figure 1: Computed tomography (left), positron emission tomography (middle) and fused PET/CT (right) images of a 75-year-old male patient with a malignant neuroendocrine tumor showed abnormally high focal fluorine-18-fluorodeoxyglucose uptake in the left thyroid lobe (maximum standardized uptake value = 4.2). Papillary thyroid carcinoma was confirmed by fine-needle aspiration biopsy

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Figure 2: Computed tomography (left), positron emission tomography (middle) and fused PET/CT (right) images of a 52-year-old female patient with unknown primary tumors showed abnormal focal fluorine-18-fluorodeoxyglucose uptake in the right lower lobe of the thyroid (maximum standardized uptake value = 3.0). Benign pathology was confirmed by fine-needle aspiration biopsy

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The mean SUV max of the malignant thyroid lesions was higher than that of the benign thyroid lesions, but no statistical difference was found (P > 0.05). [Table 1] shows the comparisons of PET/CT findings between benign and malignant focal thyroid lesions incidentally detected on PET/CT.
Table 1: Comparisons of PET/CT findings between benign and malignant focal thyroid lesions incidentally detected on 18F-FDG PET/CT

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 » Discussion Top


Thyroid incidentalomas are discovered at a high rate as modern diagnostic imaging modalities such as ultrasonography (USG), CT and magnetic resonance imaging are becoming an integral part of clinical evaluations. [2],[14] The wide use of PET/CT in the examination of cancer patients may provide an additional contribution to this high prevalence. [15],[16],[17] When focally increased 18 F-FDG uptake is detected in the anterior neck, it is important to define whether the lesion corresponds to the thyroid, lymph node or other organs. The dual modality of PET/CT provides significant benefits over PET alone, including unambiguous localization and characterization of the lesion. [16] In this study, we retrospectively reviewed 2000 18 F-FDG PET/CT scans performed at our institute between April 2011 and October 2012. Our data showed a 2.9% prevalence of incidental focal thyroid FDG uptake on 18 F-FDG PET/CT, which is within the range of 1.2-4.3% as reported in the literature. [1],[2],[3],[4],[5],[15],[16],[17],[18]

Because thyroid nodules are not rare, it is important to identify which nodules are at risk for malignancy. The cancer risk of focal thyroid lesions detected on 18 F-FDG PET/CT was found to be 35% in our study, which is similar to other reported data. [1],[2],[3],[10] This high risk of malignancy supports the performance of a further diagnostic procedure, such as USG and FNAB, in subjects with focal thyroid lesions on PET/CT. It has been suggested that SUV measurements as a semiquantitative indicator can discriminate between benign and malignant tumors; [1],[3],[16],[19],[20],[21],[22] focal thyroid lesions with a high SUV max had a high likelihood of malignancy. However, it is not rare to see moderate FDG uptake by malignant thyroid lesions and high uptake by benign thyroid lesions. [2],[4] Our data are very similar to previous reports showing that the uptake of 18 F-FDG may be prominent in benign thyroid lesions (e.g., thyroiditis). [6] Although a high uptake of 18 F-FDG has been reported for some high-grade thyroid carcinomas, certain well-differentiated papillary carcinoma of the thyroid may show a low uptake of 18 F-FDG. [4],[23],[24] The reason for the conflict between the 18 F-FDG uptake results and the SUV max characteristics between the benign and malignant lesions may be that the SUV max is influenced by various factors. SUV max positively correlates with the proliferation ability (glucose transporter expression), increased blood flow and the diameter of malignant tumors. [20] No other explanation for the discrepancy has been given until now.

In this study, the mean SUV max value for the malignant thyroid lesions was higher than that for benign thyroid lesions. However, we did not find a significant difference in the SUV max between benign nodules and malignant lesions (P > 0.05). There were some overlapping cases; one benign thyroid lesion confirmed by histopathological evaluation had a SUV max of 3.03 and one malignant thyroid lesion (papillary thyroid cancer) had a SUV max of 2.40. Except for this case, all thyroid cancers had higher SUV max values (SUV max ≥ 2.5) than the benign lesions. In this study, because the sample size was small, we failed to identify a reliable cutoff value for SUV max to differentiate between malignant and benign thyroid lesions. More data are needed to clarify the role of SUV max in the differentiation of benign and malignant thyroid lesions incidentally identified on PET/CT. Thus, in our opinion, the diagnosis should not rely only on the measured SUV max value. Therefore, new criteria other than the SUV max are necessary to improve the accuracy in characterizing focal thyroid lesions on PET.

Published reports have suggested that CT characteristics such as calcification and the lesion size of the nodules may be useful in distinguishing malignant lesions from benign ones. [25] Ultrasound is a more sensitive diagnostic modality for differentiating benign from malignant thyroid lesions because ultrasound has a higher spatial resolution than CT. [26],[27],[28] However, in our retrospective study group, thyroid USG was performed only in a minority of patients. The reason for the limited sonographic data is that our clinicians believe that the CT characteristics of thyroid lesions are sufficient. Our CT images have provided more precise information on the localization, calcification status and lesion size of the nodules. The size of the malignant thyroid lesions was significantly larger than that of the benign thyroid lesions (P < 0.05), and calcification was detected in 4 malignant thyroid lesions and only in 2 benign thyroid lesions. Our results indicate that the CT findings associated with a SUV max analysis may be helpful for characterizing focal thyroid lesions that are incidentally found by PET/CT.

The 18 F-FDG accumulation may vary in the normal TG, causing misinterpretation of FDG PET images. [6],[7],[29] Some authors believe that diffuse or focal moderate to intense FDG uptake in the TG may be normal. The mechanism of the 18 F-FDG uptake in the normal TG is not exactly clear and thyrocytes use glucose as well as free fatty acids. [6],[7] Diffusely increased 18 F-FDG uptake in the TG is generally considered benign as most cases are chronic thyroiditis or Graves' disease. [2],[16] However, focal PET incidentaloma indicates a thyroid nodule, such as adenoma or cancer. [20] Some studies have shown that focal FDG uptake of the TG may be malignant in 14-57% of cases. [3],[10],[17] The initial diagnostic evaluation of a suspicious thyroid lesion routinely involves FNAB with or without sonographic guidance. FNAB is a relatively sensitive and specific test with a false-negative rate ranging from 0.7% to 2.4% and a false-positive rate as low as 0% and it carries accuracy of 95% when guided by imaging. [1],[19] We did not evaluate the lesions with diffuse increased 18 F-FDG uptake in the TG in our retrospective study because these lesions are likely to be benign. Our data are consistent with the literature; in our study, malignant lesions in 7 cases (35%) with focal uptake and benign lesions in 7 cases (35%) with focal uptake have been detected by pathological examination. [1],[2],[3],[10] This indicates that a focal 18 F-FDG uptake pattern on PET/CT might be associated with a benign condition, similar to a diffuse 18 F-FDG uptake pattern. However, these focal lesions are at risk for containing malignancy and it is important to conduct a further detailed evaluation.

The importance of accurate imaging of regional lymph nodes is well-recognized because lymph node metastases impact the disease-free and specific survival times. Lymph node metastases are usually diagnosed by pre-operative USG of the regional neck lymph nodes. [30],[31] Jeong et al. compared the diagnostic accuracy of 18 F-FDG PET/CT to that of USG for the pre-operative evaluation of CLN status in patients with papillary thyroid cancer. The study concluded that FDG-PET/CT did not provide additional benefits over USG for lateral neck lymph node metastases. [31] In our study, the numbers of CLNs with malignant and benign thyroid lesions were similar. Because of the limited number of CLNs, we could not evaluate the diagnostic accuracy of 18 F-FDG PET/CT for the CLN status in patients with malignant thyroid lesions. We were also unable to differentiate the increased focal uptake in the lymph nodes as malign or benign without histopathological confirmation.


 » Conclusion Top


High focal 18 F-FDG uptake in the TG may be associated with an increased risk of malignancy, but the clinical significance is yet unclear. More data are needed to elucidate the role of SUV max in the differentiation between benign and malignant thyroid lesions and to determine a useful cut-off level for SUV max . If an increased focal uptake of 18 F-FDG is present in the TG on PET/CT, a prompt histopathological evaluation should be suggested for definitive diagnosis.

Limitations

This study had several limitations. Because of the retrospective design, FNAB evaluation was not performed in two-thirds of the focal incidental thyroid lesions with high 18 F-FDG uptake detected on PET/CT. USG was not performed for these lesions. Low dose whole body CT with a PET/CT scanner is relatively inferior to diagnostic CT for the evaluation of the thyroid lesion characteristics. In additional, the relatively small sample size was another limitation; however, many previous studies had similarly small sample sizes. [2],[17],[20],[32]

 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]

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