We collected the clinical, laboratory and ultrasound retrospective data of 200 subjects (119 females and 81 males, 174 benign and 26 malignant nodules) younger than 18 years-old with thyroid nodules (Table 2). The overall rate of malignancy (ROM) observed was 13%, which rises up to 26% if nodules with a diameter greater than 1 cm were considered. The mean age at diagnosis was 11.6 years-old (range 2-18), with a mean duration of follow-up of 8.6 years. Female to male ratio was 1.47, dropping to 1.27 by considering malignant nodules.
Familial anamnesis for autoimmune thyroid disease was positive in 108/200 (53.9%), while 69/200 subjects (34.6%) had autoimmune thyroid disease. Radiation exposure due to previously radiotherapy-treated cancer was present in 28/200 (14.1%) of subjects. No risk factors were found in 35/200 (17.3%) of cases. Regarding the risk factors investigated, no difference was observed among benign and malignant nodules.
Laboratory data showed mean TSH levels of 2.01 mcUI/ml (0.1-5.3), mean fT4 levels of 11.5 pg/ml (1.05-31.4), and mean fT3 levels of 4.09 pg/ml (2.3-4.6). TSH levels was significantly lower in subjects with a benign nodule than in subjects with a malignant nodule, being 1.94 mcUI/ml (0.1-4.9) vs 2.56 mcUI/ml (0.86-5.3), respectively (p=0.01). No differences were observed for fT4 and fT3 levels or for the presence of anti-peroxidase and anti-thyroglobulin antibodies.
Ultrasound evaluation showed the localization of the nodule in the right lobe in 92 subjects (46%), the involvement of the left lobe in 91 subjects (45.5%) and the bilateral localization in 17 (8.5%). Bilateral and right lobe involvement was associated with a higher malignancy rate than left lobe localization (23.6% vs 18.5% vs 5.5% malignancy rate, respectively, p=0.01). Intranodal vascularization was present in 61/200 (30.4%), while intranodal calcification in 23/200 (11.5 %); both were associated with higher malignancy rate (p=0.003 and p=0.009, respectively), as well as lymph node involvement (p<0.0001) A larger nodule diameter was significantly more present in the malignant nodule than in the benign nodule group (mean diameter 24 mm vs 8 mm, respectively, p=<0.001). The hypoechoic pattern was the most frequently observed ultrasound feature for both groups, with no correlation with the rate of malignancy.
When considering the indeterminate cytology category, no differences were observed in terms of age, gender, family history, genetic mutations, radiation exposure, thyroid hormone profile and ultrasound pattern, as well as the presence of intranodal calcifications or vascularization (Table 3). Localization of the nodule in the right lobe and larger diameter were associated with a higher rate of malignancy (p=0.01 and p<0.003 respectively), as well as lymph node involvement (p<0.0001).
Of the 174 subjects with benign nodules, 125 were evaluated by periodical clinical and ultrasound check, FNAB was performed in 49 subjects, whereas 14 underwent to surgery.
FNAB was performed on the basis of nodule size and ultrasound feature in 75/200 (37.5%) of subjects, including 7 TIR1 (9.3%), 4 TIR1c (5.3%), 22 TIR2 (29.3%), 14 TIR3a (18.7%), 9 TIR3b (12%), 3 TIR4 (4%) and 16 TIR5 (21.4%) (Table 4).
Surgery was performed in 40/200 (20%), with a total malignancy rate of 65% (0% for the TIR1-TIR3a, 77.8% for the TIR3b and 100 % for the TIR4-TIR5 categories).
Of the 14 subjects with cytological category TIR3a, 6 underwent surgery, 5 by lobectomy, with a histological diagnosis of thyroid adenoma, and 1 by total thyroidectomy, with histological diagnosis of multinodular struma. The mean duration of follow-up was 4.6 years and FNAB was repeated in the remaining 8 subjects every 12-18 months, with confirmation of the cytological category.
All subjects with indeterminate TIR3b category underwent surgery; 7 of them underwent total thyroidectomy, with final diagnosis of papillary DTC in 5 cases, follicular DTC in 1 case and papillary microcarcinoma in 1 case, while the remaining 2 subjects underwent lobectomy, with final diagnosis of multinodular struma.
All subjects with cytological categories TIR4-TIR5 underwent total thyroidectomy and histological analysis confirmed a papillary DTC in all cases.
The total accuracy of FNAB was 95%. For the benign low-risk categories TIR1-TIR2 and the malignant categories TIR4-TIR5 the FNAB showed 100% accuracy, whereas for indeterminate categories TIR3a and TIR3b accuracy was 100% and 77.8% respectively. The sensitivity and specificity of FNAB for all categories was 92.3% and 92.6%, respectively.