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this process are unknown.

Tumor types and uptake patterns
[63]
Papillary thyroid cancer accounts for nearly 90% of all cases of thyroid carcinomas . Primary thyroid
carcinomas would be expected to make up the majority of thyroid incidentalomas, however it is important
to recognize that metastases and thyroid lymphomas have also been described. This is significant as it may
prompt a change in prognosis and treatment. A meta-analysis identified 1.1% of PET-detected thyroid
incidentalomas to represent metastatic disease and a 19.8% overall malignancy rate (with 15.4% representing
[64]
papillary thyroid carcinoma) . Metastases to the thyroid were described with solitary focal, multiple focal,
and diffuse patterns of FDG avidity . Table 2 includes tumor types diagnosed by either cytopathology or
[65]
histopathology in studies reporting this information.

IMAGING CHARACTERISTICS
Although generally uncommon, focal thyroid incidentalomas are reported at higher frequencies than diffuse
lesions, and the associated rate of malignancy is greater. Therefore, imaging characteristics, such as the
magnitude of FDG uptake, have been postulated to adjust for malignancy risk.

Standardized uptake value
Standardized uptake values (SUV) are commonly reported to quantify the magnitude of FDG uptake on
PET/CT. Several studies have evaluated the ability of SUV to discriminate malignant from benign thyroid
max
[66]
incidentalomas with conflicting conclusions (see Table 3). Mitchell et al. reported that using a SUV
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cutoff value of 5.0 resulted in 60% sensitivity and 91% specificity for detection of malignancy, while
Boeckmann et al. proposed a cutoff value of 4.2. Some reports noted a significant difference in SUV
[67]
max
between malignant and benign lesions (albeit frequently with substantial overlap), while others showed no
difference at all. Recall that benign and malignant oncocytic/Hürthle cell lesions are known to exhibit high
FDG-avidity due to an intrinsic mitochondrial defect resulting in inefficient glucose metabolism [22,23] .

Small tumors, including many thyroid incidentalomas, may not be accurately quantified on PET imaging
[68]
due to the partial-volume effect . It is generally thought that the limit of resolution for PET/CT uptake is
5-8 mm, although the partial volume effect may impact SUV values in lesions measuring 2 to 3 times the
spatial resolution. Measures such as metabolic tumor volume (MTV) have attempted to correct for this
limitation by accounting for volume, which may allow greater accuracy in the assessment of metabolic
activity and thus the risk of malignancy. Unfortunately, data regarding these parameters remains
inconclusive in their ability to discriminate benign from malignant thyroid incidentalomas. A study by
Ceriani et al. evaluated functional PET-derived measures and found that malignant lesions had
[25]
significantly higher values of MTV, total lesion glycolysis (TLG = MTV × SUV mean ), SUV , SUV mean , and
max
SUV . Of these, TLG was the most useful parameter as it correctly identified 79% of lesions (univariate
peak
logistic regression, P < 0.0001).

The study by Ceriani et al. also employed radiomic analysis of these lesions, using quantitative data from
[25]
medical imaging to glean additional information such as shape and texture analysis. A multivariate stepwise
logistic regression analysis found that TLG, SUV , and shape sphericity remained significant (P < 0.0001).
max
All triple-positive tumors were found to be malignant, while 93% of triple-negative lesions were benign. A
recent study by Aksu et al. supports these findings with the development of a predictive model combining
[69]
SUV and a radionomic parameter noted as GLRLM RLNU . GLRLM describes heterogeneity of the lesion and
max
was found to have the highest AUC value on ROC analysis. The resulting model was found to have a
sensitivity and specificity of 75% and 81.8%, respectively. Other studies support the utility of these measures