Ultrasound criteria (EU-TIRADS) to identify thyroid nodule malignancy risk in adolescents. Correlation with cyto-histological findings.

INTRODUCTION: Thyroid nodule (TN) harbouring a thyroid carcinoma are more common in paediatric than adult patients. In paediatric population, the evaluation of a TN should require specific paediatric tools for its diagnostic and therapeutic management. High-resolution ultrasonography and cytological evaluation after fine-needle aspiration biopsy (FNAB) remain the cornerstones of evaluation of TN. OBJECTIVES: To evaluate in paediatric TN for the first time the usefulness and precision of the ultrasound criteria defined by the "Thyroid Imaging Reporting and Data System (EU-TIRADS) 2017 in adults" to establish the ultrasound indication for the practice of FNAB and stratify the risk of malignancy. PATIENTS AND METHODS: 24 paediatric patients under age 18 years with thyroid nodules were attended in the last 15 years, 24 of them (31 nodules; age: 15.2 ±â€¯2.2 years; 18 women) met the inclusion criteria: FNAB with Bethesda classification and ultrasound with EU-TIRADS score. EU-TIRADS score were evaluated retrospectively. Fourteen patients underwent surgery and the definitive histological diagnosis was obtained, this allowed the calculations of sensitivity, specificity and positive and negative predictive values of the EU-TIRADS and Bethesda classification. Data on the largest diameters of the nodules were collected. RESULTS: Of the overall 31 nodules, the distribution by EU-TIRADS (T) category was: T1 (3.2%), T2: 2 (6.4%), T3: 7 (22.6%), T4: 16 (51.6%) and T5: 5 (16.1%). All malignant nodules were included in EU-TIRADS category 4 or 5. By the other hand, 13 of the 25 benign nodules were also included in the EU-TIRADS 4 category, and one in the 5. The distribution by categories of Bethesda's classification (B): BI: 6 (19.4%), BII: 14 (45.2%), BIII: 5 (16.1%), BIV: 2 (6.5%), BV: 0 and BVI: 4 (12.9%). The pathological diagnosis of the 14 patients who underwent surgery was: 6 papillary carcinomas and 8 with benign lesions: 6 nodular hyperplasia and 2 follicular adenoma. The percentage of malignancy was 42%. The sensitivity of the EU-TIRADS classification to detect malignant nodules was 100%, the specificity was 25%, PPV 44% and NPV 100%. The sensitivity of the Bethesda classification to detect malignant nodules was 86%, the specificity was 75%, PPV 67% and NPV 90%. The analysis of the largest diameter of the nodules did not show statistically significant differences between benign and malignant lesions. CONCLUSIONS: EU-TIRADS for ultrasonographic criteria classification in combination with the clinical history is an adequate and reproducible method to estimate suspicion of malignancy of paediatric TN. It is also a reliable diagnostic tool to decide which nodules will be candidates for FNAB.

Ultrasound criteria (EU-TIRADS) to identify thyroid nodule malignancy risk in adolescents. Correlation with cyto-histological findings. / Criterios ecográficos (EU-TIRADS) para identificar el riesgo de malignidad de los nódulos tiroideos en adolescentes. Correlación con los hallazgos cito-histológicos.

INTRODUCTION: Thyroid nodule (TN) harboring a thyroid carcinoma are more common in pediatric than adult patients. In pediatric population, the evaluation of a TN should require specific pediatric tools for its diagnostic and therapeutic management. High-resolution ultrasonography and cytological evaluation after fine-needle aspiration biopsy (FNAB) remain the cornerstones of evaluation of TN. OBJECTIVES: To evaluate in pediatric TN for the first time the usefulness and precision of the ultrasound criteria defined by the"Thyroid Imaging Reporting and Data System (EU-TIRADS) 2017 in adults" to establish the ultrasound indication for the practice of FNAB and stratify the risk of malignancy. PATIENTS AND METHODS: 24 pediatric patients under age 18 years with thyroid nodules were attended in the last 15 years, 24 of them (31 nodules; age: 15.2 ± 2.2 years; 18 women) met the inclusion criteria: FNAB with Bethesda classification and ultrasound with EU-TIRADS score. EU-TIRADS score were evaluated retrospectively. Fourteen patients underwent surgery and the definitive histological diagnosis was obtained, this allowed the calculations of sensitivity, specificity and positive and negative predictive values of the EU-TIRADS and Bethesda classification. Data on the largest diameters of the nodules were collected. RESULTS: Of the overall 31 nodules, the distribution by EU-TIRADS (T) category was: T1 (3.2%), T2: 2 (6.4%), T3: 7 (22.6%), T4: 16 (51.6%) and T5: 5 (16.1%). All malignant nodules were included in EU-TIRADS category 4 or 5. By the other hand, 13 of the 25 benign nodules were also included in the EU-TIRADS 4 category, and one in the 5. The distribution by categories of Bethesda's classification (B): BI: 6 (19.4%), BII: 14 (45.2%), BIII: 5 (16.1%), BIV: 2 (6.5%), BV: 0 and BVI: 4 (12.9%). The pathological diagnosis of the 14 patients who underwent surgery was: 6 papillary carcinomas and 8 with benign lesions: 6 nodular hyperplasia and 2 follicular adenoma. The percentage of malignancy was 42%. The sensitivity of the EU-TIRADS classification to detect malignant nodules was 100%, the specificity was 25%, PPV 44% and NPV 100%. The sensitivity of the Bethesda classification to detect malignant nodules was 86%, the specificity was 75%, PPV 67% and NPV 90%. The analysis of the largest diameter of the nodules did not show statistically significant differences between benign and malignant lesions. CONCLUSIONS: EU-TIRADS for ultrasonographic criteria classification in combination with the clinical history is an adequate and reproducible method to estimate suspicion of malignancy of pediatric TN. It is also a reliable diagnostic tool to decide which nodules will be candidates for FNAB.

Follicular Thyroid Carcinoma Metastases on Round Ligament of Liver.

ABSTRACT: We describe a case of a 69-year-old woman with follicular thyroid cancer of long evolution, with thyroidectomy 20 years before, who had remained clinically stable until now, when she started to present abnormal levels of serum thyroglobulin. An 123I whole-body scan showed a high uptake in the upper right half of her abdomen, and an 18F-FDG PET/CT located this focus at the liver's round ligament. Pathology findings after surgery showed the focus to be a differentiated thyroid cancer metastasis. This is an unusual presentation of differentiated thyroid cancer metastasis.

Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity.

Autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto thyroiditis (HT), are the most prevalent organ-specific autoimmune diseases, but their pathogenesis is still incompletely understood. The PD-1/PD-L1 pathway is an important mechanism of peripheral tolerance that has not been investigated in AITDs. Here, we report the analysis of the expression of PD-1, PD-L1 and PD-L2 in PBMCs, infiltrating thyroid lymphocytes (ITLs) and in thyroid follicular cells (TFCs) in GD, HT and multinodular goiter (MNG) patients and healthy controls PBMCs (HC). By combining flow cytometry, tissue immunofluorescence and induction experiments on primary and thyroid cell line cultures, we show that: 1) while PD-1+ T cells are moderately expanded in PBMCs from GD vs HC, approximately half of T cells in the infiltrate are PD-1+ including some PD-1hi; 2) PD-L1, but not PD-L2, is expressed by 81% of GD glands and in 25% of non-autoimmune glands; 3) PD-L1, was expressed by TFCs in areas that also contain abundant PD-1 positive T cells but; 4) co-localization in TFCs indicated only partial overlap between the smaller areas of the PD-L1+ and the larger areas of HLA class II+ expression; 5) IFNγ is capable of inducing PD-L1 in >90% of TFCs in primary cultures and cell lines. Collectively these results indicate that the PD-1/PD-L1 axis is operative in AITD glands and may restrain the autoimmune response. Yet the discrepancy between easy induction in vitro and the limited expression in vivo (compared to HLA) suggests that PD-L1 expression in vivo is partially inhibited in GD and HT glands. In conclusions 1) the PD-1/PD-L1 pathway is activated in AITD glands but probably not to the extent to inhibit disease progression and 2) Thyroid autoimmunity arising after PD-1/PD-L1 blocking therapies in cancer patients may result from interfering PD-1/PD-L1 tolerance mechanism in thyroid with minimal (focal) thyroiditis. Finally acting on the PD-1/PD-L1 pathway could be a new approach to treat AITD and other organ-specific autoimmunity in the future.

One-step nucleic acid amplification for intraoperative analysis of sentinel lymph node in papillary thyroid carcinoma.

Objective Lymphadenectomy in papillary thyroid carcinoma (PTC) is controversial. It is indicated whenever metastases have been proven before or during surgery and as a prophylactic treatment in high-risk patients. However, 30-50% of cN0 patients become pN1 postoperatively. In PTC, selective-sentinel-lymph-node-biopsy (SLNB) with conventional intraoperative analysis is 8% false negative. One-step nucleic acid amplification (OSNA) is a molecular technique which allows real-time detection of mRNA encoding for cytokeratin 19. OSNA has been introduced in intraoperative analysis of several tumors to reduce false-negative rates and distinguish micrometastasis from macrometastasis. Our objective was to evaluate the impact of the introduction of OSNA in the intraoperative evaluation of the sentinel node (SN) in PTC. Design We analyzed a series of 35 patients subjected to SLNB. Methods All the dissected nodes, SN and non-SN, were evaluated with OSNA and cytology. Results We obtained a total of 110 SN. SLNB proved positive in 14 patients (40%) with cytology and in 23 (65.7%) with OSNA (P < 0.001). In the 29 patients with subsequent lymphadenectomy we obtained 360 lymph nodes ((52 positive in cytology (14.4%) and 107 in OSNA (29.7%)). Lymphadenectomy proved positive in 16 patients according to cytology (55%) and in 24 according to OSNA (83%) (P = 0002). The majority of patients with micrometastasis in SN showed only micrometastasis in lymphadenectomy. Conclusions The present study shows selective-sentinel-lymph-node-biopsy with one-step nucleic acid amplification technique to be feasible in papillary thyroid carcinoma. The quantitative nature of one-step nucleic acid amplification paves the way toward a more personalized surgical approach, limiting lymphadenectomy to patients with intraoperative evidence of macrometastasis in the sentinel node.