The prevalence of thyroid nodules in the general adult population is up to 60%. Thyroid malignancy accounts for approximately 1–10% of incidental thyroid nodules (Fisher and Perrier 2018; Durante et al. 2018). Ultrasonography allows the assessment of various morphological features suggesting malignancy. European Thyroid Imaging and Reporting Data System (EU-TIRADS) features include irregular margins, non-oval shape, microcalcifications and hypoechogenicity (Russ et al. 2017). Thyroid scintigraphy is used to determine the functional status of a nodule as non-functioning nodules are associated with a 10 to 20% risk of malignancy, while most hyperfunctioning nodules are benign (Maia and Zantut-Wittmann 2012). Both morphological and functional features help to select nodules for US-guided FNAB. However, results are inaccurate in approximately 10 to 30% of cases (Maia and Zantut-Wittmann 2012).
SSTR are highly expressed at the surface of neuroendocrine cells and can be found in many tissues, including normal thyroid tissue (Özgüven et al. 2021). Beyond expression in NETs, expression of SSTR was also demonstrated in other tumors such as lymphoma, small cell lung carcinoma and prostate cancer or benign lesions such as sarcoid granulomas (Banerjee and Pomper 2013). SSTR expression can be detected by scintigraphy and PET/CT using radiolabeled somatostatin analogues such as 111In-octreotide and 68Ga-DOTATATE, respectively.
Increased thyroid uptake on SSTR imaging has been described in various thyroid disorders such as Hashimoto's thyroiditis, papillary thyroid cancer and medullary thyroid cancer (Lincke et al. 2009). In a retrospective study, thyroid uptake was evaluated in 237 patients who underwent 68Ga-DOTATATE PET/CT to localize unknown primary and metastatic neuroendocrine tumors (Nockel et al. 2016). Among fourteen patients with incidental focal thyroid uptake, three (21%) had papillary thyroid cancer. No malignancy was detected among the remaining eleven patients, including six patients (42%) with adenomatous nodules and one patient (7%) with lymphocytic thyroiditis.
In the present case, the incidental finding of a high focal thyroid uptake with a SUVmax of 13.8 as detected by 68Ga-DOTATATE PET/CT raised suspicion for thyroid malignancy. Histopathological and immunohistochemical analyses revealed a benign adenomatous nodule with overexpression of SSTR2. Remarkably, the high density of SSTR2 was predominantly localized in endothelial cells. High endothelial expression of SSTR has been reported in both malignant and benign lesions such as lymphoma, hemangioma and thymoma (Ruuska et al. 2018; Brogsitter et al. 2014; Ferone et al. 2001). The presence of SSTR on endothelial cells is thought to contribute to tissue growth, however, precise clinical significance remains unclear (Watson et al. 2001).