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Page 2 of 19 Corn et al. J Cancer Metastasis Treat 2021;7:41 https://dx.doi.org/10.20517/2394-4722.2021.63

INTRODUCTION
The relatively rapid development and diffusion of medical imaging technology have afforded tremendous
benefits in the non-invasive evaluation of many benign and malignant lesions. Most forms of diagnostic
imaging showed a growth rate of 2- to 6-fold between 2000 and 2016 in both the United States and Ontario,
[1]
Canada , a trend expected worldwide. Imaging studies may be performed for a multitude of reasons, such
as screening, staging, or surveillance of cancerous and noncancerous diagnoses. While studies may be
undertaken for a specific and targeted purpose, the possibility of unveiling incidental lesions cannot be
ignored. The likelihood of revealing an incidental finding varies substantially (< 5% to 22%) depending on
the chosen imaging modality .
[2]
The primary concern of an incidentally discovered lesion, commonly termed an incidentaloma, relates to
the associated risk of malignancy. While all imaging modalities may unveil incidentalomas, the metabolic
data afforded by functional imaging such as F-FDG PET/CT may provide further information to decipher
18
the clinical relevance of such lesions. F-FDG is a glucose analog that shows uptake levels corresponding to
18
glycolysis rates and glucose consumption. It is frequently elevated in cancerous tissues due to inefficient
[3]
aerobic glycolysis (termed the Warburg effect) . Physiologic FDG uptake is reported in brown fat, skeletal
muscle, lymphoid tissue, and the thymus . Multiple benign etiologies, primarily inflammatory or infectious
[4]
in origin, may also exhibit uptake due to increased rates of glucose metabolism . Studies reveal a 1.2%-
[5,6]
1.7% overall detection rate of unexpected malignancies or premalignant lesions in patients undergoing
PET/CT evaluation .
[7,8]
Furthermore, second primary malignancies were described in 4.1%-8.5% of PET/CT scans completed for
staging or surveillance purposes [8-10] . Interestingly, some studies describe a higher likelihood of
incidentalomas in patients undergoing PET/CT for screening purposes (3.0%-3.1%) compared to the
evaluation of known or suspected cancer (1.9%-2.3%) [11,12] . Given the estimated 2 million PET/CT scans
performed annually in the United States, these small fractions add up to a significant number of lesions that
must be addressed.

Incidentally discovered lesions in the thyroid are uncovered in 21%-34% of ultrasound examinations [13-15]
and 16% of CT or MRI scans [16,17] . Among these lesions, the risk of malignancy is reported to range from
1.5%-11% [18,19] . On PET scans, the thyroid gland exhibits very low physiologic FDG avidity. However this is
typically less than the background blood pool and is usually not clearly visualized on the whole-body fusion
[5]
PET/CT images , which aligns with the observation that the primary energy substrate for the thyroid is free
fatty acids [20,21] . In contrast, oncocytic/Hürthle cell lesions (both benign and malignant) are known to exhibit
FDG-avidity due to an intrinsic mitochondrial defect that results in inefficient glycolytic metabolism [22,23] . In
addition, thyroid malignancies, such as papillary, follicular, and anaplastic carcinomas and thyroid
lymphoma, may also be expected to exhibit increased FDG uptake due to increased glucose metabolism.

Incidental FDG-avid uptake in the thyroid gland exists in two predominant patterns - focal and diffuse. The
overall detection rate of thyroid incidentalomas on PET/CT, irrespective of uptake patterns, is estimated at
1.5%-4.2% [8,18,24-36] . Most reports attribute a risk of malignancy of 5.1%-22.0% of these PET-detected thyroid
[37]
incidentalomas [8,28,31,33,35] , notably higher than those detected by ultrasound or CT . Similar rates of thyroid
incidentaloma detection and associated malignancy are noted amongst those undergoing surveillance of a
[38]
known cancer and the general population undergoing screening with PET/CT .

In this review, we will first discuss the abnormal patterns of FDG uptake in the thyroid gland and the
associated risk of cancer, and the types of cancers diagnosed. Next, we will describe specific imaging features