scholarly journals Somatic genetic alterations in a large cohort of pediatric thyroid nodules

2019 ◽  
Vol 8 (6) ◽  
pp. 796-805 ◽  
Author(s):  
Barbora Pekova ◽  
Sarka Dvorakova ◽  
Vlasta Sykorova ◽  
Gabriela Vacinova ◽  
Eliska Vaclavikova ◽  
...  
Keyword(s):  
High Frequency ◽  
Detection Rate ◽  
Thyroid Nodules ◽  
Pediatric Patients ◽  
Distant Metastases ◽  
Genetic Alterations ◽  
Papillary Thyroid ◽  
Benign Lesions ◽  
Benign Nodules ◽  
Generation Sequencing

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.

scholarly journals Hashimoto Thyroiditis and Thyroid Ultrasound: A Prospective Study

2021 ◽  
Author(s):  
Anabela Zunino ◽  
Claudia Vazquez ◽  
Laura Delfino ◽  
Adriana Reyes ◽  
Alicia Lowenstein
Keyword(s):  
Prospective Study ◽  
Thyroid Nodules ◽  
Thyroid Volume ◽  
Hashimoto Thyroiditis ◽  
Needle Aspiration ◽  
Thyroid Peroxidase ◽  
Papillary Thyroid ◽  
Immunological Activity ◽  
Benign Nodules ◽  
A Prospective Study

Abstract Purpose We performed a prospective study in patients with positive thyroid peroxidase antibodies (TPOAb), to describe their ultrasound (US) patterns and the prevalence of thyroid nodules. Methods In 195 consecutive patients, with positive TPOAb, thyroid US was performed by the same physician and equipment and categorized into four echographic patterns (EP). We determined the prevalence of thyroid nodules and their etiology confirmed by cytology or histology. Results The median TPOAb was 526 IUI/ml. EP1 or normal US was present in 9,7%; EP2 or early/indeterminate stage in 29,4%; EP3 or established thyroiditis in 45,4% and EP4 or advanced/late stage in 15,5% of the patients. TPOAb (median = 857 UI / ml) (p = 0.001), TSH and thyroid volume ​​were higher in EP3. A higher degree of fibrosis was associated with TPOAb > 1000 IU/ml(p = 0,003). Thyroid nodules were reported on US at 47,2% of HT. Fine needle aspiration(FNA) was performed in 49/60 nodules. Cytology: BII: 41 patients (83,7%), B V: 1 patient (2%): suspicious for lymphoma; B VI: 3 patients(6,1%) : Papillary thyroid carcinoma. Benign cytology was present in 56% of EP3 (p = 0,048). Conclusions Higher TPOAb, TSH levels, and thyroid volume were associated with EP3. Fibrosis correlated with TPOAb > 1000 IU/ml. In our population, benign nodules were associated with established thyroiditis patterns. The increased inflammation and immunological activity of Hashimoto thyroiditis (HT) could be a favorable environment for growth factors for benign nodular development.

scholarly journals Three-dimensional telomere profiles in papillary thyroid cancer variants: a pilot study

2021 ◽  
Author(s):  
Aline Rangel-Pozzo ◽  
Tinuccia Dettori ◽  
Daniela Virginia Frau ◽  
Federica Etzi ◽  
John Gartner ◽  
...  
Keyword(s):  
Pilot Study ◽  
Telomere Length ◽  
Thyroid Nodules ◽  
Genome Instability ◽  
Three Dimensional ◽  
Papillary Thyroid ◽  
Benign Lesions ◽  
Related Genome ◽  
Follicular Variant ◽  
Follicular Thyroid Adenoma

Papillary thyroid carcinoma (PTC) has two main histologic variants: classical-PTC (CL-PTC) and follicular variant PTC (FV-PTC). Recently, due to its similar features to benign lesions, the encapsulated FV-PTC variant was reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Nonetheless, specific molecular signatures are not yet available. It is well known that telomere-related genome instability is caused by inappropriate DNA repair of dysfunctional telomeres and that mechanisms involved in the damaged telomere repair processing may led to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). There was no association between BRAF expression and telomere length in all tested samples. Our data indicate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles FTA. NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and that telomere length of NIFTP overlaps with that of the FTA histotype. These preliminary findings reinforce the view that NIFTP are lesions closer to non-malignant thyroid nodules and confirmed that short telomeres are a feature of PTC.

Interobserver Agreement of Planar and SPECT Tc99m-MIBI Scintigraphy for the Assessment of Hypofunctioning Thyroid Nodules

2019 ◽  
Vol 58 (03) ◽  
pp. 258-264
Author(s):  
Simone Schenke ◽  
Rigobert Klett ◽  
Peter Acker ◽  
Thomas Rink ◽  
Michael C Kreissl ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Interobserver Agreement ◽  
Thyroid Nodules ◽  
Study Cohort ◽  
Papillary Thyroid ◽  
Planar Images ◽  
Benign Nodules ◽  
Different Levels ◽  
Mibi Scintigraphy ◽  
Spect Images

Abstract Introduction Thyroid scintigraphy with 99mTc-methoxyisobutylisonitrile (MIBI) is a helpful tool for the risk stratification of thyroid nodules (TN). Whereas a nodule with low or hypointense MIBI uptake has a low risk for malignancy, a hyperintense uptake may indicate a malignant nodule, which requires surgical resection. The appropriate diagnostic or therapeutic regimen of an isointense nodule with an uptake similar to the paranodular tissue is discussed controversially. Aim of this study was to assess the interobserver agreement (IA) for the assignment of TN to the three categories: hypo-, iso-or hyperintense. Methods Retrospective analysis of planar and SPECT images of MIBI scintigraphy was performed in 36 randomly selected patients with hypofunctioning TN and histological diagnosis. Four observers with different levels of experience in MIBI-scintigraphy analyzed MIBI uptake and assigned the nodules to the appropriate category. To assess the IA, Fleiss‘ Kappa was calculated. Results The study cohort included 11 patients with papillary thyroid carcinoma (diameter 20.3 mm) and 25 patients with benign nodules (diameter 24.8 mm). The IA for all nodules using planar images was 0.76 compared to 0.80 for SPECT images. The IA was better in the subgroup of malignant nodules for planar images as well as SPECT images (Kappa 0.91 and 0.90, respectively) compared to benign nodules (0.65 and 0.76, respectively). Using SPECT images, only one thyroid carcinoma presented with hypointense uptake, the remainder with hyper- or isointense uptake. In contrast, benign nodules were found in all categories. Conclusion MIBI scintigraphy shows a good IA for the interpretation of thyroid carcinoma. The IA is further improved if MIBI scintigraphy is performed in SPECT technique.

scholarly journals OR28-05 Approaching Indeterminate Thyroid Nodules in the Absence of Molecular Markers. “The BETH-TR Score”

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Subramanian Kannan ◽  
Kranti Khadilkar ◽  
Shivaprasad Kumbenahalli Siddegowda
Keyword(s):  
Molecular Markers ◽  
Thyroid Nodules ◽  
High Volume ◽  
Easy Access ◽  
P Value ◽  
Papillary Thyroid ◽  
Thyroid Cancers ◽  
The Mean ◽  
Roc Area ◽  
Benign Nodules

Abstract Context: Given the lack of easy access to molecular markers, for indeterminate thyroid nodules (Bethesda (BETH) category III, IV), the clinician can either decide to get a second opinion from an expert high volume thyroid cytopatholgist, re-do the FNAC after a period of 3-6 months or send the patient for a diagnostic hemithyroidectomy. Reviewing the sonographic risk features is also one way of triaging these nodules. The ACR-TIRADS (TR) is an objective method of sonographic risk assessment and is superior to other forms of sonographic classification. Aim: We propose combining the scoring of TR category and BETH category (both expressed as numerical value and summated) and look at the score which could potentially guide the clinician in deciding whom to send for surgery. Settings and Design: Observational Prospective collection of consecutive patient data from Thyroid FNAC clinic. Statistical analysis used: The BETH categories were represented numerically and summated with the TR category. The categorical outcome variables of Benign and Malignant nodules and the summated score was analysed using Kruskal-Wallis test. Results: We analysed 450 FNAC data, out of which 403 were thyroid nodule aspirates. Out of these nodules, 96 of them underwent surgery and 64% of these nodules were malignant on final histopathology (Malignant=62 and Benign=34). The mean (sd) size of the benign nodules was 3.6 (2.2)cm compared to 2.8 (1.8)cm of the malignant nodules. After excluding those with BETH 1 (n=4), the mean BETH-TR score for benign nodules was 6(1.4) and malignant nodules 9.4(2.1) (p<0.0001). The BETH-TR score progressively increased from 7.3(0.92) in Follicular thyroid cancers (FTC) to 8.6(1.4) in Follicular variant Papillary thyroid cancer (FVPTC) to 10(1.3) in classic Papillary thyroid cancers (PTC). Among the indeterminate nodules (BETH III & IV; n=40), the BETH-TR score of benign nodules was 6.75(1) and malignant nodules was 7.5(0.72) (p value=0.01). A BETH-TR score >=7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases (Likelihood ratio 3.5; ROC area: 0.8841; CI 0.79-0.94). Conclusion: A combined sono-cytological BETH-TR score is one way to triage management of indeterminate thyroid nodules. A BETH-TR score >=7 gave a sensitivity of 92% specificity of 74% and correctly identified malignant nodules in 86% of cases.

The thyroid risk score (TRS) for nodules with indeterminate cytology

2021 ◽  
Vol 28 (4) ◽  
pp. 225-235
Author(s):  
Carla Colombo ◽  
Marina Muzza ◽  
Gabriele Pogliaghi ◽  
Sonia Palazzo ◽  
Guia Vannucchi ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Risk Score ◽  
Thyroid Nodules ◽  
Point Mutations ◽  
Roc Curves ◽  
Cost Effective ◽  
Genetic Alterations ◽  
Gold Standard Method ◽  
Risk Of Malignancy ◽  
Benign Nodules

Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25–30% of them are classified as indeterminate. We aimed to set up a ‘thyroid risk score’ (TRS) to increase the diagnostic accuracy in these cases. We prospectively tested 135 indeterminate thyroid nodules. The pre-surgical TRS derived from the sum of the scores assigned at cytology, EU-TIRADS classification, nodule measurement, and molecular characterization, which was done by our PTC-MA assay, a customized array able to cost-effectively evaluate 24 different genetic alterations including point mutations and gene fusions. The risk of malignancy (ROM) increased paralleling the score: in the category >4 and ≤ 6 (low suspicion), >6 ≤ 8 (intermediate suspicion), and >8 (high suspicion); ROM was 10, 47 and 100%, respectively. ROC curves selected the score >6.5 as the best threshold to differentiate between malignant and benign nodules (P < 0.001). The TRS > 6.5 had a better performance than the single parameters evaluated separately, with an accuracy of 77 and 82% upon inclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among malignant or benign cases, respectively. In conclusion, for the first time, we generated a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities, for the differential diagnosis of indeterminate nodules. The combination of different parameters reduced the number of false negatives inherent to each classification system. The TRS > 6.5 was highly suggestive for malignancy and retained a high accuracy in the identification of patients to be submitted to surgery.

scholarly journals MON-504 VEGFA and VEGFR2 Expression in Different Histological Types of Thyroid Nodules: Could Immunohistochemistry Have a Clinical Utility?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Natassia Elena Bufalo ◽  
Karina Colombera Peres ◽  
Larissa Teodoro ◽  
Paulo Latufi-Filho ◽  
Icleia Siqueira Barreto ◽  
...  
Keyword(s):  
Protein Expression ◽  
Clinical Utility ◽  
Thyroid Nodules ◽  
Vascular Endothelial ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Tall Cell ◽  
Benign Nodules ◽  
Endothelial Growth Factors ◽  
Current Guidelines

Abstract Vascular endothelial growth factors (VEGFs) are a family of proteins involved in several elements that play an important role in the development of blood vessels. Besides acting in angiogenesis, VEGFA has important roles in chemotaxis, for macrophages and granulocytes, and vasodilation. VEGFA binds to VEGFR2, that acts on the MAPK and PI3K pathways, fundamental pathways for thyroid carcinogenesis. In order to assess the expression of VEGFA and VEGFR2, in different thyroid nodules, we used a Tissue MicroArray including 91 benign (74 females, 16 males, 49.84±12.65years old) and 125 malignant thyroid nodules (97 females, 28 males, 46.57±14.87 years old). Clinical and pathology data were obtained from 47 goiters; 43 follicular adenomas (FA) and a total of 104 papillary thyroid carcinomas (PTC), including 35 classic papillary thyroid carcinomas (CPTC), 30 follicular variant of PTC (FVPTC), 25 oxifilic variant of PTC (OVPTC), 14 tall cell papillary thyroid carcinomas (TCPTC); and 21 follicular thyroid carcinomas (FTC). All patients were managed according to a standard protocol based on current guidelines and followed-up for 116.9±70.8 months. VEGFA protein expression did not differentiate benign from malignant thyroid nodules. However, VEGFA was more frequently expressed in the less differentiated thyroid tissues. In fact, 95.8% of the FTC had positive expression. On the contrary, the intensity of this protein expression was progressively lower according to the process of cellular dedifferentiation (Goiter: 21.4%; FA: 16.3%; PTC: 8.7% and FTC: 0.0%; x2 = 0.031). There was no difference in VEGFR2 expression between malignant and benign nodules (x2= 0.108), but this protein showed more intense expression in tissues that also presented Hürthle cells (x2 &lt;0.0001). We were not able to find any correlation, neither of VEGFA nor with VEGFR2 expression, and any other feature of aggressiveness, including invasion, metastasis, lymph node metastasis, and distant metastasis. We conclude that VEGFA and VEGFR2 expression may help identify less differentiated tumors and the analysis of a larger cohort may prove the clinical utility of these markers.

scholarly journals Evaluation of characteristics of thyroid nodules on contrast-enhanced ultrasonography: a retrospective analysis of 252 cases

2020 ◽  
Vol 22 (2) ◽  
pp. 164
Author(s):  
Wen Luo ◽  
Xiao Yang ◽  
Jiani Yuan ◽  
Lina Pang ◽  
Peidi Zhang ◽  
...  
Keyword(s):  
Retrospective Review ◽  
Thyroid Nodules ◽  
Contrast Enhanced Ultrasound ◽  
Diagnostic Specificity ◽  
Benign Lesions ◽  
Predictive Values ◽  
Contrast Enhanced ◽  
Contrast Enhanced Ultrasonography ◽  
Benign Nodules ◽  
Sensitivity Specificity

Aim: This study investigated the enhancement patterns observed on contrast-enhanced ultrasound (CEUS) images for differentiating thyroid nodules.Material and methods: A retrospective review was conducted of CEUS cine loops of 252 nodules by two independent readers. Seven categories of enhancement patterns were identified: concentric hypoenhancement; heterogeneous hypoenhancement; hypoenhancement with sharp margin; homogeneous hyper/isoenhancement; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. Associations between these patterns and the confirmed pathological/cytological outcomes (178 malignant, 74 benign) were analyzed and the sensitivity, specificity and positive predictive values (PPVs) determined. The agreement of the readers’ assessments was evaluated by Kappa value.Results: For malignant nodules, the predominant 3 patterns were: concentric hypoenhancement, heterogeneous hypoenhancement and homogeneous hyper/isoenhancement. For each of these, the diagnostic specificity was above 87% and the PPV more than 85%. Combining these patterns for malignancy the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 96.1% (98.9%), 71.6% (71.6%), and 89.1% (89.3%), respectively. For benign nodules, the predominant 4 patterns were: hypoenhancement with sharp margin; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. The specificity for each was above 98% and the PPV more than 70%. Combining these patterns for benignity, the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 71.6% (71.6%), 96.1% (98.9%) and 88.3% (96.3%), respectively. The inter-reviewers agreement for classifying enhancement patterns was excellent (κ = 0.84, 95% CI: 0.79-0.89).Conclusions: Enhancement patterns of thyroid nodules on CEUS investigation, enable differentiation between malignant and benign lesions with good diagnostic sensitivity, specificity and PPV.

scholarly journals Study of BRAF and RAS Mutations in Thyroid Nodules with Indeterminate Cytology and Papillary Thyroid Cancer

2020 ◽  
Vol 1 (2) ◽  
pp. 105-112
Author(s):  
Abd ELmogheth Madani Sahar ◽  
◽  
Gotsiridze Irine ◽  
Keyword(s):  
Decision Making ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Thyroid Nodules ◽  
Genetic Alterations ◽  
Genetic Change ◽  
Braf V600e ◽  
Secondary Outcome ◽  
Papillary Thyroid ◽  
Indeterminate Cytology

OBJECTIVES Thyroid cancer Treatment decision-making is often guided by tumor tissue molecular analysis. The aim of this study was the detection of BRAF, NRAS and HRAS mutations in Georgian patients with thyroid cancer and determination of the frequency of these mutations in the respective populations. SETTING Diagnostic molecular laboratory located in Tbilisi, Georgia. PARTICIPANTS 116 patients with thyroid cancer participated in the study. PRIMARY AND SECONDARY OUTCOME MEASURES Genetic change is the main force of thyroid tumor development, based on new methods of managing thyroid cancer. The latest significant genetic discovery in thyroid cancer is the BRAF-T1799A (V600E) transformation (the gene for B-type RAF kinase, BRAF). Since the initial report of this breakthrough in thyroid cancer years ago, rapid progress has been made. The BRAF mutation is the most common genetic change in thyroid cancer. BRAF and NRAS mutations are frequent genetic alterations found in thyroid nodules. These molecular markers establish a differential diagnosis and facilitate clinical decision-making. Prevalence of thyroid nodule-associated mutations has not been studied in Georgia. We evaluated BRAF, NRAS and HRAS mutations in Georgian patients with indeterminate cytology or diagnosed with papillary thyroid cancer (PTC). RESULTS BRAF (V600E), NRAS (G12C, G12D, Q61R, and Q61K) and HRAS (G12C, G13R, and Q61R) were determined in the DNA extracted from fine needle aspirate specimens. In total, 116 patient samples were analyzed using competitive-specificTaqMan PCR (Cast PCR TM). In these samples, 36 were diagnosed as papillary thyroid carcinoma, and 80 were indeterminate by Bethesda system for reporting thyroid cytopathology (BSRTC III-V). BRAF (V600E) mutation was the most frequent genetic alteration found in 31% of all analyzed samples. Specifically, this mutation was present in 61% of PTC cases and 18% of cases classified as indeterminate (BSRTC III-V). NRAS mutations were present in 16% of PTC and 30% of indeterminate cytology samples. NRAS G12D and Q61R were most prevalent at 36.6% and 40% of all NRAS mutations. BSRTC IV category of indeterminate cytology had the highest frequency of NRAS mutations at 43%. From analyzed samples, HRAS (Q61R) mutation was present in only one PTC case.

scholarly journals Value of Contrast-Enhanced Ultrasound in Partially Cystic Papillary Thyroid Carcinomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Fengkai Fang ◽  
Yi Gong ◽  
Liyan Liao ◽  
Fei Ye ◽  
Zhongkun Zuo ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Univariate Analysis ◽  
Contrast Enhanced Ultrasound ◽  
Papillary Thyroid ◽  
Thyroid Carcinomas ◽  
Intensity Index ◽  
Peak Intensity ◽  
Contrast Enhanced ◽  
Heterogeneous Enhancement ◽  
Benign Nodules

Partially cystic papillary thyroid carcinomas (PCPTCs) are rarely reported papillary thyroid carcinomas (PTCs) and are usually misdiagnosed as benign nodules. The objective of this study was to provide the various sonographic characteristics of partially cystic thyroid nodules for differentiation between malignant and benign nodules, including those for conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Twenty-three PCPTC patients and 37 nodular goiter patients were enrolled in this study. We evaluated the size, cystic percentage, solid echogenicity, calcification, vascularity, and CEUS parameters for each nodule. The final diagnosis of all patients was confirmed via surgery. Univariate analysis demonstrated that compared with benign nodular goiters, PCPTCs more frequently presented with calcification, hypoechogenicity of the solid part, hypoenhancement, heterogeneous enhancement, centrifugal perfusion, peak intensity index &lt;1, time to peak index ≥1, and area under the curve index &lt;1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that heterogeneous enhancement, centrifugal perfusion, and peak intensity index &lt;1 are independent CEUS characteristics related to malignant PCPTCs and can be used for their differentiation from benign nodular goiters (all p &lt; 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to distinguish malignant PCPTCs from benign thyroid nodules.

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