:: KJR :: Korean Journal of Radiology

This study investigated diagnostic values of semi-quantitative parameters assessed by 18F-FDG PET/CT for differentiation of malignant from benign thyroid 18F-FDG incidentaloma. Results revealed that various semi-quantitative parameters (i.e., SUVmax, MTV, and TLG) assessed by 18F-FDG PET/CT were different between malignant and benign thyroid 18F-FDG incidentaloma, that could contribute to differentiation of malignant from benign thyroid 18F-FDG incidentaloma. Our study also revealed that semi-quantitative parameters (i.e., SUVmax, MTV, and TLG) were not significantly different within pathological subtypes of primary malignant thyroid 18F-FDG incidentaloma.

Thyroid incidentalomas on FDG PET/CT are currently a subject of major interest because of emerging practical use of FDG PET/CT in cancer evaluation. Prevalence of thyroid incidentaloma on FDG PET/CT is reported to be approximately 1.1–4.0% (8, 9, 11, 17, 18, 19). According to recent meta-analysis investigating 147505 units, the pooled incidence of thyroid incidentalomas detected by FDG PET/CT was 2.46%, malignancy ratio was 34.6% (20). In this study, thyroid incidentalomas on FDG PET/CT were identified with prevalence of 1.9% (99/5216) and the malignancy ratio was 64.6% (64/99). Prevalence of malignant thyroid incidentaloma was higher than reported in previous studies, which has been between 26.7 and 50% (8, 9, 11, 17, 18, 19, 20). This discordance may be related to excluding patients with diffuse thyroid FDG PET uptake in this study.

This considerably high prevalence of malignancy justifies further work-up, such as ultrasound and ultrasound-guided FNAB. Although FNAB is the most accurate and cost-effective method for evaluating thyroid nodules, accuracy of FNAB depends mainly on skill and experience of the investigator and cytopathologist. It is essential to differentiate malignant from benign thyroid 18F-FDG incidentaloma by 18F-FDG PET/CT because of wide use of FDG PET/CT in clinical practice. The role of FDG PET/CT in the differentiating diagnosis of thyroid 18F-FDG incidentaloma is under debate. Several studies reported higher SUVmax in malignant lesions than in benign ones (5, 19) and a positive correlation between presence of SUVmax > 5.0 and diagnosis of malignancy (5). Ho et al. (21, 22) found a significantly higher average value of SUVmax in malignant thyroid lesions, but the authors were unable to establish an optimal SUVmax cutoff value to differentiate benign from malignant lesions, because there was considerable overlap in SUVmax between malignant and benign thyroid 18F-FDG incidentalomas. This overlap makes it difficult to use SUVmax to differentiate malignant from benign thyroid 18F-FDG incidentaloma. However, a number of studies revealed no significant difference in SUVmax between benign and malignant nodules (9, 17, 21). Our study revealed malignant thyroid incidentalomas had higher SUVmax than benign. Results of ROC curve analysis revealed that a threshold SUVmax of 4.45 had 90.6% sensitivity and 68.6% specificity for identifying malignant thyroid incidentalomas.

Metabolic tumor volume and TLG are measurements of metabolic activity of tumors determined by 18F-FDG PET/CT images (23). Unlike SUVmax, that reflects only the point of greatest metabolic activity within the tumor, volume based metabolic parameters of MTV could potentially have clinical value in evaluation of tumor biology, evaluation of response to treatment, and prognostication in various cancers (24). TLG, calculated by multiplying the SUV mean by the MTV (25), has been suggested to better reflect global metabolic activity in whole tumors (25). TLG has potential to become a valuable imaging biomarker in prognostic studies on human solid tumors, adding value to clinical staging, as well as in treatment response assessment and treatment optimization (24). However, few published studies have adapted these quantitative indexes for differentiating malignant from benign thyroid 18F-FDG incidentaloma and the conclusion is under debate (15, 16). In the Kim et al. (15) study, patients with higher serum TSH levels (TSH > 1.31 mIU/mL), malignant thyroid 18F-FDG incidentaloma revealed statistically significantly higher MTV 4.0 compared with benign ones. However, MTV 3.5, MTV 3.0, and MTV 2.5 revealed no statistical differences between malignant and benign thyroid 18F-FDG incidentaloma (15). In comparison ROC curve analysis, no significant difference was detected between SUVmax and MTV 4.0 in prediction of malignant thyroid 18F-FDG incidentaloma. However, the combination of SUVmax and MTV 4.0 improved predictive value compared with individual AUCs of SUVmax and MTV 4.0 (15). Kim and Chang (16) reported no significant difference in MTV and TLG between malignant and benign thyroid 18F-FDG incidentalomas. Our study revealed malignant thyroid 18F-FDG incidentaloma had statistically significantly higher MTV indexes (including MTV 4.0, MTV 3.5, MTV 3.0, and MTV 2.5) and TLG indexes (including TLG 4.0, TLG 3.5, TLG 3.0, and TLG 2.5) compared with benign ones. In comparison ROC curve analysis, MTV 4.0 has highest performance (85.9% sensitivity and 71.4% specificity, AUC = 0.872) of differentiating malignant from benign thyroid 18F-FDG incidentaloma in all MTV indexes, TLG 4.0 has highest performance (81.3% sensitivity and 94.3% specificity, AUC = 0.895) in all TLG indexes. TLG 4.0 revealed highest performance for differentiating malignant from benign thyroid 18F-FDG incidentaloma with highest AUC in all semi-quantitative parameters assessed by 18F-FDG PET/CT. AUC (TLG 4.0) were significantly larger than AUC (SUVmean), AUC (MTV 2.5), AUC (MTV 3.0), AUC (MTV 3.5), AUC (TLG 2.5) and AUC (TLG 3.0), respectively. There were no significant statistical difference between AUC (TLG 4.0) and AUC (SUVmax), AUC (MTV 4.0), or AUC (TLG 3.5). Results from Kim and Chang's study are discordant with our study (16). This discordance may be related to composition of the study sample. Malignancy ratio was 64.6% (64/99) in our study sample, but only 24.5% (49/200) in Kim and Chang's study sample (16). Their study also revealed malignant incidental thyroid lesions had higher 18F-FDG PET/CT parameters including SUVmax, MTV, and TLG than benign, but there was no statistical difference.

This retrospective single center study has limited sample size of thyroid incidentaloma patients. We did not include diffuse thyroid FDG PET uptake because previous reports indicate that the majority represent chronic thyroiditis or diffuse thyroid autonomy and do not need histological diagnosis, except for a small number of conditions (26). Additional, VOI selection is essential for determining tumor MTV. Several different methods for VOI selection could be used: manually defined VOI, iso-contour VOIs based on a fixed percentage of the SUVmax, and iso-contour VOIs based on a fixed SUVmax threshold. This study used the fixed SUVmax threshold method, that may be subject to issues arising from SUV variability. Therefore, to minimize issues, we used various thresholds of SUVmax for VOI selection.

Conventional quantitative PET parameters only derived from 18F-FDG PET/CT were not adequate to differentiate benign from malignant thyroid incidentalomas. To overcome this, the Hounsfield unit ratio of thyroid nodules was assessed compared to the contralateral thyroid lobe on non-contrast CT to stratify further risk of malignancy in thyroid incidentalomas detected in 18F-FDG PET/CT (27). Dual-time-point 18F-FDG PET/CT and retention index were used in differential diagnosis of thyroid incidentaloma (28). Barrio et al. (29) measured SUVmax, thyroid to background thyroid lesion SUVmax/thyroid background SUVmean (TL/TBG), thyroid to blood pool TL/blood pool SUVmean (BP), and thyroid to liver TL/liver SUVmean (L) ratios in benign and malignant lesions to test if intense focal 18F-FDG thyroid uptake is associated with malignancy. These studies revealed various methods may significantly improve accuracy of PET/CT for differentiating benign from malignant focal thyroid lesions.

In conclusion, this study has revealed that volume-based PET/CT parameters such as TLG and MTV combining tumor volume and metabolic activity of the entire tumor, could potentially have clinical value in differential diagnosis of thyroid incidentaloma along with SUVmax. Considering that the measurement of volume-based PET parameters required additional time and effort to the measurement of SUVmax, the clinical value of volume-based PET functional parameters in differential diagnosis of thyroid 18F-FDG incidentaloma should be further determined in future prospective studies with a large sample size, and combined CT pattern analysis are also needed.