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Background: The role of minimal extrathyroidal extension (mETE) as a risk factor for persistent papillary thyroid carcinoma (PTC) is still debated. The aim of this study was to assess the clinical impact of mETE as a predictor of worse initial treatment response in PTC patients and to verify the impact of radioiodine therapy after surgery in patients with mETE. Methods: We reviewed all records in the Italian Thyroid Cancer Observatory (ITCO) database and selected 2237 consecutive patients with PTC who satisfied the inclusion criteria (PTC with no lymph node metastases and at least 1 year of follow-up). For each case, we considered initial surgery, histological variant of PTC, tumor diameter, recurrence risk class according to the American Thyroid Association (ATA) risk stratification system, use of radioiodine therapy, and initial therapy response, as suggested by ATA guidelines. Results: At 1-year follow-up, 1831 patients (81.8%) had an excellent response, 296 (13.2%) had an indeterminate response, 55 (2.5%) had a biochemical incomplete response, and 55 (2.5%) had a structural incomplete response. Statistical analysis suggested that mETE (odds ratio [OR] 1.16, p=0.65), tumor size >2 cm (OR 1.45, p=0.34), aggressive PTC histology (OR 0.55, p=0.15), and age at diagnosis (OR 0.90, p=0.32) were not significant risk factors for a worse initial therapy response. When evaluating the combination of mETE, tumor size, and aggressive PTC histology, the presence of mETE with a >2 cm tumor was significantly associated with a worse outcome (OR 5.27, 95% CI, p=0.014). The role of radioiodine ablation in patients with mETE was also evaluated. When considering radioiodine treatment, propensity score-based matching was performed, and no significant differences were found between treated and non-treated patients (p=0.24). Conclusions: This study failed to show the prognostic value of mETE in predicting initial therapy response in a large cohort of PTC patients without lymph node metastases. The study suggests that the combination of tumor diameter and mETE can be used as a reliable prognostic factor for persistence and could be easily applied in clinical practice to manage PTC patients with low-to-intermediate risk of recurrent/persistent disease.

Serum thyroglobulin (Tg) stimulation by recombinant human TSH (rhTSH), in combination with neck ultrasonography (US), is an important tool in the first follow-up of differentiated epithelial cell thyroid carcinoma (DTC) patients. The objective of this study was to investigate if a second rhTSH stimulation, performed 2-3 years later, is of clinical utility in the follow-up of these patients.One hundred and one consecutive ambulatory DTC patients were studied. The great majority of them (89/101) were low-risk patients, being stage I or II at tumor node metastasis (TNM) staging classification. All study patients had been treated by surgery and radioiodine ablation, and exhibited, at first rhTSH follow-up, either undetectable Tg (or=1 ng/mL) (rhTSH1-Tg-, n = 89 patients considered as free of disease) or low Tg (1-5 ng/mL) (rhTSH1-Tg+, n = 12 patients considered with uncertain prognosis), with no US evidence of residual disease. In all patients, serum Tg measurement after a second rhTSH stimulation and neck US were performed.At the second follow-up, all 89 rhTSH1-Tg-patients showed a negative US, and Tg became low positive only in one case, whereas it remained undetectable in the other patients. The overall negative predictive value of rhTSH1-Tg- was, then, 98.9%. Out of the remaining 12 patients (i.e., rhTSH1-Tg+ patients), 2 showed disease persistence/recurrence (with a positive predictive value of rhTSH1-Tg+ of 16.7%) and 6 became Tg-.A second rhTSH stimulation is useless in DTC patients who were rhTSH-Tg and imaging negative at first follow-up, while it is suggested in patients with detectable, although low, rhTSH-Tg levels at first follow-up: in the absence of clinical or US evidence of disease persistence, these patients should not be retreated by radioiodine, but simply scheduled for a later rhTSH stimulation.

Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivo regulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes.We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed.In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS.These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans.