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uptake. Similar observations on the impact of radiotherapy on the emergence of the diffuse thyroidal uptake
[27]
were made by Hassan et al. .
The risk of malignancy in patients found to have diffuse thyroidal uptake on PET scan is very low, with a
quoted range of 0.6%-3.5% in the literature [5,57] . In a recent systematic analysis of 26 published articles
encompassing 2255 cases, only one patient of differentiated thyroid cancer without thyroiditis displayed a
diffuse thyroidal uptake. While in 4 other cases, differentiated thyroid cancer was present alongside
thyroiditis. In addition, primary thyroid lymphoma was diagnosed in 10 cases .
[5]

Diffuse-plus-focal FDG uptake (see example, Figure 3)
Diffuse-plus-focal uptake describes the simultaneous occurrence of 1 or more focal FDG-avid thyroid
[16]
lesions on a background of diffuse uptake, which was first described in 2006 by Choi et al. , who identified
and reported this FDG thyroidal uptake variant in five patients among their 1763 subjects, yielding a
prevalence of 0.28%. None of these 5 patients had malignancy, while three patients were judged to have
chronic thyroiditis based on pathology (n = 2) and ultrasound imaging (n = 1). The preliminary conclusion
was that a diffuse-plus-focal FDG uptake pattern might have the same clinical significance as a diffuse
18
pattern.

Kurata et al. studied 1626 subjects who underwent PET scanning and unveiled 4 patients exhibiting the
[46]
diffuse-plus-focal uptake (prevalence 0.24%). Two patients were confirmed to have papillary thyroid
carcinoma associated with Hashimoto’s thyroiditis, while the other two had adenomatous goiter associated
[35]
with Hashimoto’s thyroiditis. More recently, Sencan Eren et al. published the results of their prospective
study of 4202 patients, uncovering this diffuse-plus-focal pattern in 13 (prevalence 0.309%). Twelve of the
latter group had adequate investigations allowing the recognition of malignancy in four (33.3%).

Thus, we presently have limited published data on this group of patients with simultaneous focal and diffuse
uptake. However, it would appear that the diffuse component here is most often attributable to benign
entities, especially chronic lymphocytic thyroiditis. The underlying pathology of the focal component would
appear to be more heterogeneous, including benign Hashimoto’s thyroiditis, adenomatous goiter and
thyroid malignancy. It is well-established that the thyroid parenchyma is diffusely heterogenous in
Hashimoto’s thyroiditis, and formation of focal lymphocytic thyroiditis nodule may occur in some
[16]
patients [59,60] . This schema may have been operative in the five patients of Choi et al. . On the other hand,
[35]
[46]
the findings of Kurata et al. and Sencan Eren et al. underscore the increased risk for malignancy in this
subset of patients with diffuse-plus-focal uptake. Further data are needed for proper management guidance.
But meanwhile, it is our view that patients with the diffuse-plus-focal uptake should be investigated in a
manner similar to patients with focal uptake.

Progression of focal to diffuse thyroid uptake
This entity is extremely rare, having been described in a single case report, but is very challenging in need to
differentiate malignant metastatic disease from benign thyroiditis. Thuillier et al. reported the case of a
[61]
49-year-old man presenting with cerebral metastasis of unknown primary, and the F-FDG PET/CT scan
18
disclosed an incidental left focal thyroid uptake, while the thyroid ultrasound was considered consistent
with thyroiditis. Upon the diagnosis of lung adenocarcinoma, pembrolizumab treatment was initiated. A
follow-up PET/CT scan revealed the progression of focal thyroid uptake to an intense diffuse uptake
(SUV 18.2). A fine-needle aspiration biopsy of the thyroid parenchyma indicated a diffuse involvement
max
from lung adenocarcinoma.