ORIGINAL RESEARCH |
https://doi.org/10.5005/jp-journals-10002-1477 |
Thyroid Incidentalomas on 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography: A Tertiary Care Hospital Experience in South India
1–4,8Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India
5,10Department of Endocrine Surgery, Christian Medical College, Vellore, Tamil Nadu, India
6,7Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India
9Department of Radiology, Christian Medical College, Vellore, Tamil Nadu, India
Corresponding Author: Julie Hephzibah, Department of Nuclear Medicine, Christian Medical College, Vellore, Tamil Nadu, India, Phone: +91 4162282176, e-mail: drjulsan@gmail.com
Received: 17 August 2022; Accepted: 05 January 2025; Published on: 06 March 2025
ABSTRACT
Thyroid incidentalomas on fluorine-18-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET-CT): A tertiary care hospital experience in South India.
Aim: To find the prevalence and clinical significance of unexpected focal uptake of 18F-FDG or nodules in the thyroid gland of consecutive PET-CT studies. To find the maximum standardized uptake value (SUVmax) of benign and malignant thyroid incidentalomas in FDG-avid lesions.
Materials and methods: A total of 2,699 18F-FDG-PET-CT studies from January to December 2018 were reviewed. Studies with incidental focal 18F-FDG uptake with SUVmax, sonography, cytology, and histopathological results were compiled and analyzed. FDG nonavid thyroid nodules on CT were also studied.
Results: In 312/2,699 patients with thyroid nodules, 18F-FDG uptake was identified in 139 (5%)—focal (76) and diffuse (63). In the cases with focal uptake, 42 were further evaluated, of which ultrasound (USG) showed thyroid imaging reporting and data system (TIRADS) 2/3 in 21 cases, TIRADS 4/5 in 20 cases, and 1 patient underwent surgery. Final histopathological examination (HPE) was suggestive of papillary thyroid carcinoma. The mean SUVmax in malignant nodules (20.20) was significantly higher (p < 0.03) than benign nodules (6.12), but there was considerable overlap (benign: 3.75–10.25; malignant: 3.34–48.32) between them. Among FDG nonavid nodules (173), only 24 were followed up with sonography [7/24 (29.16%) had TIRADS 4/5 lesions]. Only 2/173 were diagnosed with malignancy.
Conclusion: Thyroid incidentalomas, though infrequent, showing 18F-FDG uptake should be evaluated with sonography followed by biopsy/fine needle aspiration (FNA) if required, to rule out malignancy. The SUVmax value was significantly lower in benign incidentalomas compared to malignant nodules; however, there was no clinically useful SUVmax cutoff value to determine malignancy due to considerable overlap between them.
Clinical significance: Thyroid carcinomas detected by 18F-FDG-PET-CT are more aggressive than those detected by other imaging modalities. From our study, we found that there is a prevalence of at least 5% of thyroid incidentalomas. Therefore, understanding the importance of further steps in evaluation is needed to avoid unnecessary investigations and also to avoid missing the possibility of detecting malignancy. This study also stated that having a cutoff value for SUVmax is ambiguous in differentiating between benign and malignant nodules.
Keywords: 18F-fluorodeoxyglucose positron emission tomography–computed tomography, Diffuse, Focal, SUVmax, Thyroid incidentalomas
How to cite this article: Benjamin J, Hephzibah J, Mathew D, et al. Thyroid Incidentalomas on 18F-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography: A Tertiary Care Hospital Experience in South India. World J Endoc Surg 2024;16(2):32–35.
Source of support: Nil
Conflict of interest: Dr MJ Paul is associated as the Editorial Board member of this journal and this manuscript was subjected to this journal’s standard review procedures, with this peer review handled independently of this editorial board member and his research group.
INTRODUCTION
The term “thyroid incidentaloma” refers to a thyroid lesion incidentally found on an imaging study or during an operation not related to the thyroid gland. With the growing use of various imaging systems, clinically inapparent thyroid lesions are being found. Thyroid carcinomas detected by fluorine-18-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET-CT) are more aggressive than those detected by other imaging modalities.
As 18F-FDG-PET-CT is extensively used in the evaluation of responses to treatment in several malignancies,1 the incidence of thyroid 18F-FDG incidentalomas is increasing.2,3 Needless operations can be reduced if there is a good differentiation between benign and malignant nodules, which also helps to prognosticate the patient. Conventional imaging techniques have difficulty in distinguishing benign from malignant findings.
AIM
To determine the prevalence and clinical implications of unanticipated focal or diffuse uptake of 18F-FDG or nodules in the thyroid gland of consecutive PET-CT studies.
To determine the maximum standardized uptake value (SUVmax) of benign and malignant thyroid incidentalomas in FDG-avid lesions.
MATERIALS AND METHODS
A total of 2,699 18F-FDG-PET-CT studies from January to December 2018 were reviewed retrospectively. Studies with unanticipated focal or diffuse 18F-FDG uptake with SUVmax, sonography, cytology, and histopathological results were compiled and analyzed. FDG nonavid thyroid nodules on CT were also studied.
Procedure of Imaging with Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography
Fluorine-18-FDG PET-CT images were acquired using a standard PET-CT scanner (Siemens Biograph TruePoint 6 PET-CT). Patient preparation involved a fasting period of a minimum of 4–6 hours and a serum glucose level lower than 150 mg/dL prior to 18F-FDG administration.
PET-CT images were acquired after 45–60 minutes of injecting 18F-FDG (3.7 MBq/kg of body weight). CT images were taken in spiral mode from the vertex to mid-thigh at 110 mAs and 130 kV, with a section width of 5 mm. CT scanning data were acquired for attenuation correction and fusion of images, followed by a 3D craniocaudal PET emission scan. Whole-body imaging was acquired from the vertex to mid-thigh with arms up.
Using the attenuation-correction technique, emission images were obtained to further characterize the suspicious lesion. Data from PET using a whole-body scanner (with high resolution) with an axial field of view of 22 cm were acquired. This data underwent iterative reconstruction, after decay and scatter correction, and was reoriented in sagittal, axial, and coronal slices. The average time to image was 20 minutes.
SUVmax levels were ascertained from the lesions using Multimodality Workplace (Siemens Syngo 2009B, VE36 A SL10P25 sMMWP SPO4) by the region-of-interest (ROI) technique. Circular ROIs were drawn manually on the images in which the suspicious lesion could be delineated.
Ethical Consideration
The study with IRB Min. No. 14362 (Retro) dated 24th November 2021 was approved by the Institutional Review Board (IRB). The waiver of consent was obtained from the IRB/Ethics Committee before the commencement of the study in view of its retrospective nature.
RESULTS
In 312/2,699 patients with thyroid nodules, 18F-FDG uptake was identified in 139 (5%)—focal (76) and diffuse (63).
In the cases with focal uptake, 42 were further evaluated, of which USG showed TIRADS 2/3 in 21 cases, TIRADS 4/5 in 20 cases, and 1 patient underwent surgery. Final histopathological examination (HPE) was suggestive of papillary thyroid carcinoma.
In the 20 cases with TIRADS 4/5, >5 of them underwent surgery. Two were benign on final HPE, and 3 were malignant on final HPE. Also, there were 5 others who had extensive metastatic disease from another primary not related to the thyroid and were not further evaluated. Ten were advised follow-up based on the clinical examination findings.
The 34 cases with focal uptake were not further evaluated because of extensive metastatic disease from another primary in 13, defaulted further evaluation in 15, and no detectable lesion on CT images in 6 patients.
Only 6 patients underwent surgery; focal uptake was noted in 5, and diffuse uptake was noted in 1. Of the 5 with focal uptake who underwent surgery (all were TIRADS 4/5 on USG), 3 were malignant, and 2 had benign histopathology. In the patient with diffuse uptake, corresponding CT images showed the entire thyroid gland to be bulky with heterogeneous enhancement and a hypodense nodule with calcification in the right lobe. The USG done showed bilateral TIRADS 5 nodules with a central compartment node. The surgical histopathology revealed poorly differentiated thyroid carcinoma.
FNAC was performed in 10 patients:
Inadequate (4): 2 advised follow-up, 2 underwent surgery, both were papillary cancer.
Benign (2): 1 advised follow-up, 1 underwent surgery, reported nodular hyperplasia.
Atypia of undetermined significance (AUS) (1): advised follow-up.
Suspicious for malignancy (1): underwent surgery; HPE: adenomatous hyperplasia.
Malignancy (2): 1 had metastatic neuroendocrine carcinoma, which was negative for calcitonin, and was advised palliative chemotherapy. The 2nd underwent surgery, the biopsy of which was reported as papillary cancer.
Mean SUVmax in malignant nodules (17.94) was significantly higher (p < 0.04) than benign nodules (6.12), but there was considerable overlap (benign: 3.75–10.25; malignant: 3.27–44.39) between them (Table 1). Among 173 FDG nonavid nodules, only 24 were followed up with sonography [7/24 (29.16%) had TIRADS 4/5 lesions]. Only 2/173 were diagnosed as biopsy-proven malignancy. PET-CT studies of 4 patients with incidental thyroid uptake and their biopsy results are shown in Figures 1234.
| Benign | Malignant | |
|---|---|---|
| Mean SUVmax | 6.12 | 17.94 (p < 0.04) |
| Range | 3.75–10.25 | 3.27–44.39 |
Fig. 1: 45/M, LLL consolidation, hoarseness of voice, NPL scopy normal, left thyroid nodule SUVmax 44.39; Biopsy: FVPTC
Fig. 2: 62/F, sacral metastases. To look for primary. Thyroid SUVmax 48.32; Biopsy: PDTC
Fig. 3: 42/F, carcinoma right breast T4bN1?M1, left lobe SUV 7.35; FNA: Atypical clusters
Fig. 4: 69/F, carcinoma cervix IIIb, thyroid R 10.25, L 9.47; FNA: Thyroiditis
DISCUSSION
The prevalence of thyroid incidentaloma on FDG PET-CT is reported to be approximately 1.1–4.0%.4,7 Choi et al., in his meta-analysis of 1,47,505 cases who underwent F18 FDG PET-CT, reported the incidence of thyroid incidentalomas as 2.46%, with a malignancy rate of 34.6%.8 In a study by Choi et al. the incidence of thyroid incidentalomas on FDG PET-CT was 1.9% (99/5,216), of which 64.6% (64/99) were malignant. The comparatively high incidence (26.7–50%) could possibly be due to the fact that patients with diffuse thyroid uptake were excluded.4,8 The incidence of malignancy in patients with focal uptake who underwent further assessment was found to be 24% in a study done by Roddy et al.9
In our study, the incidence of thyroid incidentalomas was 5%. Sixteen patients had biopsy/FNA. Among them, 8/16 (50%) were malignant, 6.25% were found to have AUS, and the rest were benign.
The high FDG uptake in thyroid malignancy may be attributed to increased cellular proliferation, glycolysis, and expression of GLUT1 (glucose transport proteins).10,11 However, there may be nonspecific increased uptake in inflammatory/infectious etiology or in benign nodules that have rapid iodine turnover and secondary lymphoid tissue activation.
The usefulness of FDG-PET in differentiating a benign from a malignant thyroid lesion has been demonstrated in several studies.12 In general, malignant lesions were found to have a significantly higher SUVmax. Chen et al. highlighted the same in his study, wherein the SUV for thyroid carcinoma was higher than for a benign thyroid nodule (p = 0.012).3
It is also noted that focal 18F-FDG activity in the thyroid has a higher risk of being malignant, as opposed to diffuse thyroidal uptake, which is more likely to be benign.4,5,13,16 In our study, among the 5 patients who were detected to have malignancy, focal uptake was noted in 3 of them, and diffuse uptake was noted in the other 2 patients.
Detection of malignancy may be improved by further investigations, such as ultrasound-guided fine needle aspiration biopsy (FNAB). Although FNAB is an economical and simple method for assessing thyroid nodules, its accuracy may be limited if the experience and skill of the cytopathologist and radiologist are inadequate.
Differentiation of malignant from benign thyroid incidentalomas is important in clinical practice, and the role of FDG PET-CT in this regard is still under debate. It has been noted that, in general, benign lesions have a lower SUVmax than malignant ones.7,13 In addition, the presence of SUVmax >5.0 correlated with malignant etiology.5
Ho et al.17,18 found similar results with higher SUVmax in malignant thyroid lesions. The challenge, however, was that an optimal SUVmax cutoff value to differentiate benign from malignant lesions was not established, due to overlap in SUVmax values between malignant and benign thyroid 18F-FDG incidentalomas. This was noted in our study as well. Therefore, it shows that SUVmax might have difficulties in properly delineating malignant from benign thyroid 18F-FDG incidentalomas.
Some studies also opined that SUVmax in benign and malignant nodules did not show any significant difference.5,17 A threshold SUVmax of 4.45 had a specificity of 68.6% and sensitivity of 90.6% for detecting malignancy in thyroid incidentalomas. In our study, it was found that thyroid incidentalomas which were malignant had higher SUVmax than benign. Due to our limited sample size, ROC curve analysis was not performed to establish a threshold SUVmax.
The limitations of our study are the retrospective design in a single center and the limited sample size of thyroid incidentaloma patients.
CONCLUSION
18F-FDG avid thyroid incidentalomas should be evaluated with sonography followed by biopsy/FNA if required, to rule out malignancy. The SUVmax value was considerably lower in benign incidentalomas as compared to malignant nodules. A clinically useful SUVmax cutoff value to diagnose malignancy was not deciphered due to the overlap between the values.
Clinical Significance
Incidentalomas are quite common due to the increasing number of PET-CT scans being done these days for various indications. From our study, we found there is a prevalence of at least 5%. Therefore, understanding the importance of instances where these incidental findings should be further evaluated is essential to avoid unnecessary investigations. More importantly, we must not miss diagnosing the possibility of malignancy. This study helped to understand the steps in the evaluation of thyroid incidentalomas and also stated that having a cut-off value for SUVmax to differentiate between benign and malignant nodules might be difficult. However, malignant thyroid incidentalomas had higher SUVmax than benign.
ORCID
Justin Benjamin https://orcid.org/0000-0001-8003-4355
Shawn S Thomas https://orcid.org/0000-0003-2307-3192
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