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and their ability to discriminate benign from malignant disease, together with related mutational analysis
findings. Finally, we will provide recommendations for the evaluation and management of thyroid
incidentalomas.

PATTERNS OF FDG UPTAKE IN THE THYROID GLAND
Lesions incidentally detected on PET/CT imaging may be referred to as PET-associated incidental
[39]
neoplasms . Within the thyroid, FDG uptake has been described in focal and diffuse patterns or
combinations thereof. In general, lesions are designated as focal when the focus of uptake comprises less
than one lobe of the thyroid, although such lesions may be multifocal and thus occur bilaterally. The term
diffuse is applied when homogenous uptake is identified. Diffuse-plus-focal uptake has been described as
focal lesions overlying a background of diffuse uptake. Table 1 describes the incidence of thyroid
incidentalomas noted in selected references along with the absolute numbers of malignancies diagnosed.
Unfortunately, it is impossible to determine the true rate of malignancy in this population as a significant
proportion of patients do not undergo further investigation due to their underlying disease status.

Focal FDG uptake (see example, Figure 1)
Focal thyroid uptake is defined as FDG avidity occurring in less than one lobe of the thyroid gland , for
[24]
which we suggested the term PEToma . The prevalence of such lesions is reported in approximately 0.5%-
[18]
2.5% of PET/CT imaging studies [18,24-27,29,30,32,33,35,36,46] . Most of these studies describe a slightly higher rate of
detection of focal vs. diffuse patterns of uptake. The malignancy risk amongst the former lesions seems to be
greater, with rates ranging from 8.6%-50% [18,24-27,29,33,35,46] . In Asian countries, the rate of focal uptake has been
reported to be double that of American studies, yet the rate of cancer is unchanged .
[31]
[18]
A retrospective study of 4726 patients (6457 FDG PET/CT scans) at our institution revealed a 3.4% rate of
thyroid incidentalomas (160 of 6457 PET/CT scans). Focal uptake was noted in 2.2% (103 patients), and
uptake was diffuse in 1.2% (57 patients). Fifty patients with focal uptake underwent further workup with
imaging and/or fine-needle aspiration and cytology (FNAC), and thyroidectomy was completed in 10
patients. Nine of the ten surgical patients were ultimately diagnosed with papillary thyroid carcinoma on
final histopathology: two micropapillary carcinomas, two extrathyroidal extensions, four multifocal
involvement, and one had > 50% poorly differentiated papillary thyroid carcinoma. Thirty percent of the
PETomas that received a tissue diagnosis (FNAC and/or histology) were cancerous, which relates to 8.7% of
all focal thyroid lesions.

Amongst countries with known iodine deficiency, the frequency of focal thyroid uptake is unexpectedly
reported to be at rates lower than the average, with incidences of 1.0%-1.8% [33,48-50] . The risk of malignancy
[51]
seems similar, with cancers reported in 23%-59% of patients , and iodine supplementation programs have
done little to change these rates .
[26]
Diffuse FDG uptake (see example, Figure 2)
Diffuse FDG uptake is reported in most studies at slightly lower rates than focal uptake. However, it was
studied in Japan much earlier, more than two decades ago. Yasuda et al. investigated 1102 healthy subjects
[52]
using the F-FDG PET scan, and they detected diffuse FDG thyroidal uptake in 36 (3.26%), only one of
18
whom was found to have hypothyroidism. Furthermore, antithyroid antibodies were positive in 27 subjects,
which led these authors to conclude that diffuse thyroidal FDG uptake may be an indicator of chronic
thyroiditis.