scholarly journals Thyroid Nodules: Pathophysiological Insight on Oncogenesis and Novel Diagnostic Techniques

2014 ◽  
pp. S263-S275 ◽  
Author(s):  
J. KRÁTKÝ ◽  
H. VÍTKOVÁ ◽  
J. BARTÁKOVÁ ◽  
Z. TELIČKA ◽  
M. ANTOŠOVÁ ◽  
...  

Thyroid nodules are a very frequent pathology among common population. Despite the vast majority of them are of benign origin, the incidence of thyroid cancer is currently rather rising. Although there are several risk factors of thyroid cancer and several clinical, ultrasound, biochemical and molecular diagnostic markers, the exact mechanisms of thyroid oncogenesis and the linkage between thyroid nodule ultrasound appearance and its biological character remain unclear. While ionizing radiation is the only one well-known risk factor for thyroid cancer, the significance of some others remains unclear. The aim of our review was to discuss some not completely known pathophysiological mechanisms involved in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell proliferation, thyroid autoimmunity and pregnancy and to describe pathophysiological background of some ultrasound markers of thyroid cancer (size, echogenicity, vascularization, calcifications and stiffness). Better knowledge in this field is crucial for development of novel diagnostic techniques and therapeutic approaches. For example, the analysis of BRAF, RAS and other mutations in cytological samples may help to distinction between follicular thyroid carcinoma and follicular thyroid adenoma and may significantly decrease the number of unnecessary surgery among patients with thyroid nodules. Alternatively, the different malign cells growth, angiogenesis, destructions of thyroid follicles, reparative changes, growth retardation, fibrosis and increased interstitial fluid pressure implicate the typical ultrasound appearance of papillary thyroid cancer (hypoechogenicity, irregular vascularization, microcalcifications, stiffness) which is essential to catch the suspicious nodules on the basis of their ultrasound appearance among large amount of benign nodules.

2019 ◽  
Vol 100 (5) ◽  
pp. 242-246
Author(s):  
L. A. Timofeeva ◽  
L. B. Shubin

Objective. To provide a rationale for using sonoelastography (SEG) in the differential diagnosis of thyroid cancer (TC).Material and methods. Thirty patients with thyroid nodules of various morphological structures were examined. The authors studied the data of SEG and immunohistochemistry (IHC) with monoclonal antibodies against types III and IV collagen (they evaluated the degree of the expressed collagen fibers). Analysis of variance, ROC analysis, and logistic regression were used (by comparing with the expression of collagens) to assess the predictive ability of ultrasound.Results. The study showed that irregular and uneven contours, microcalcifications, and “the height greater than the width” were most significant among the ultrasound signs in the diagnosis of TC. Cool colors prevailed when performing SEG in the pattern of thyroid cancer. Purple-blue hues were predominantly recorded (p<0.05 with regard to benign nodules), green ones were less frequently. ROC analysis of compression elastography showed that the area under the curve was 0.785 (95% CI 0.740-0.826), sensitivity 78.1%, specificity 79.0%. Comparison of the data of IHC and SEG revealed a direct correlation of tissue elasticity with the degree of a stromal component and with the presence of collagen-containing structures.Conclusion. SEG may suppose the probable nature of thyroid nodules on the basis of their morphological features. The low degree of the stromal component and the low content of types III and IV collagen make follicular colloid goiter and adenoma soft, which is recorded at SEG. TC is characterized by a high collagen level attributable to the characteristics of the metabolism of cancer cells, which makes them solid in the mode of SEG.


2020 ◽  
Vol 10 (7) ◽  
pp. 1621-1630
Author(s):  
Xia Liu ◽  
Defeng Chang ◽  
Dan Xie

Objective: To investigate the diagnostic value of color Doppler ultrasonography in detecting calcifications in thyroid nodules for benign and malignant thyroid nodules. Methods: This study selects 108 patients with thyroid nodules who underwent color Doppler ultrasonography at designated hospitals from June 2013 to June 2018 as study subjects, retrospectively analyzes their general patient data, preoperative color Doppler ultrasound data and postoperative pathological diagnosis results, and discusses the diagnostic value of calcification rate, calcification type and calcification characteristics for benign and malignant thyroid nodules. Results: The results show that preoperative color Doppler ultrasonography found 112 thyroid nodules in 108 patients, including 72 benign nodules and 40 malignant nodules; pathological analysis confirmed 124 thyroid nodules, including 78 benign nodules and 46 malignant nodules; the diagnostic coincidence rate of color Doppler ultrasound is 90.32% (112/124), the misdiagnosis rate is 9.68% (12/124), the specificity is 86.94%, and the sensitivity is 81.27%; in these 112 thyroid nodules, 89 nodules were calcified accounting for 79.46%; in 72 benign nodules, 13 nodules were calcified accounting for 18.06%; in 40 malignant nodules, 17 were calcified accounting for 42.50%; the calcification of malignant nodules was significantly higher than that of benign nodules; in 72 benign nodules, 6 cases is coarse calcification accounting for 8.33%, 3 cases is cyclic calcification accounting for 4.16%, and cyclic and coarse calcification are only 23.46% sensitive to thyroid cancer; in 40 malignant nodules, 3 cases is coarse calcification accounting for 7.5%, and 2 cases is cyclic calcification accounting for 5.00%. Conclusions: According to the analysis, the calcification in thyroid nodules has relatively high sensitivity and specificity for the diagnosis of benign and malignant nodules and it can be used as a specific index for screening thyroid cancer.


2020 ◽  
Vol 1 (1) ◽  
pp. 14-17
Author(s):  
Lucio Mango

In recent decades was observed a gradual increase in the detection of thyroid nodules in the adult population. Given the increase in prevalence of nodules, a similar trend to the growth in the incidence of thyroid cancers was found. The reasons for this increased incidence for thyroid cancer are controversial. Increased incidence is caused by an improvement in diagnostic techniques or does not result from an overdiagnosis, but represents a real increase in the incidence of thyroid cancer? Whatever the reality, the fact of an increased incidence of thyroid cancer for certain involves problems to global health which in any case must be evaluated and corrected.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Carlo Cappelli ◽  
Ilenia Pirola ◽  
Elena Gandossi ◽  
Fiorella Marini ◽  
Alessandra Cristiano ◽  
...  

Background. Toshiba Medical System has developed a new Doppler technique [Superb Microvascular Imaging (SMI)] that has improved microvascular flow imaging. SMI depicts perinodular and intranodular thyroid microvascular flow in higher detail compared to standard colour Doppler (CD) and power Doppler (PD) imaging. Objective. Assess the nodular microvascular architecture by SMI compared to CD and PD features in a series of thyroid nodules submitted to fine needle aspiration cytology, in order to evaluate the potential of SMI in detecting thyroid cancer. Materials and Methods. From April 2016 to July 2017, 254 patients with thyroid nodules, evaluated as at high risk for malignancy in agreement with AACE/ACE/AME guidelines, were submitted to cytology. All nodules were previously submitted to ultrasound grayscale, CD, PD, and SMI evaluation. Benign and malignant nodules were stratified in accordance to the number of vessels visualised by SMI: score 1 with a maximum of two blood vessels and score 2 with three or more vessels. Results. Score 1 was found in 59.6% of benign nodules and in 17.9% of malignant nodules, whereas score 2 was found in 40.4% and in 82.1%, respectively (sensitivity 81.7%; specificity 60.5%, p<0.001). Variables significantly associated with malignancy in the univariate analysis were gender (OR, 0.18; 95% CI, 0.08-0.37; p<0.001), vascularity (OR, 1.91; 95% CI, 1.65-3.89; p<0.001), and SMI (OR, 6.72; 95% CI, 3.89-11.59; p<0.001); multivariate logistic model confirmed SMI score 2 as an independent risk factor for malignancy (OR, 6.99; 95% CI, 3.46-12.09; p<0.001). Conclusions. This prospective pilot study showed that SMI can depict intranodular flow in higher detail compared to CDI and PDI, thus improving thyroid cancer detection.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Qin ◽  
Zhenqian Yu ◽  
Haixia Guan ◽  
Liangfeng Shi ◽  
Yongping Liu ◽  
...  

Background. Despite the many studies examining thyroid cancers, the effect of thyroid autoantibodies on differentiated thyroid carcinoma (DTC) remains unclear.Objective. To investigate the association between serologic thyroid autoantibodies (ATAs) and DTC, we retrospectively evaluated data of thyroid nodules obtained from patients who underwent thyroid surgery.Methods. Data of thyroid nodules obtained from 1,638 patients who underwent thyroid surgery were evaluated. Thyroid autoimmunity was assessed by the presence of thyroglobulin (TgAb) or thyroid peroxidase antibodies (TPOAb).Results. Among our study cohort, the prevalence of elevated TgAb (≥40 IU/mL) and TPOAb (≥50 IU/mL) was higher in patients with DTC than those with benign nodules. Patients with DTC and elevated TgAb had a higher prevalence of extrathyroidal invasion. In the multivariate analysis, TgAb ≥ 40 IU/mL was significantly associated with DTC (odds ratio [OR] = 2.10, 95% confidence interval [CI] 1.40–3.15) compared with TgAb < 40 IU/mL group, independent of other confounding factors such as decreased age, single nodule, and elevated TSH level. In conclusion, elevated TgAb was associated with DTC.Conclusions. This study revealed that high levels of TgAb may act as an independent prediction factor for DTC, and suggests that patients with high TgAb concentrations may be predisposed to DTC.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3785
Author(s):  
Vincenzo Marotta ◽  
Maurizio Bifulco ◽  
Mario Vitale

Thyroid nodules are detected in up to 60% of people by ultrasound examination. Most of them are benign nodules requiring only follow up, while about 4% are carcinomas and require surgery. Malignant nodules can be diagnosed by the fine-needle aspiration cytology (FNAC), which however yields an indeterminate result in about 30% of the cases. Testing for RAS mutations has been proposed to refine indeterminate cytology. However, the new entity of non-invasive follicular thyroid neoplasm, considered as having a benign evolution and frequently carrying RAS mutations, is expected to lower the specificity of this mutation. The aggressive behavior of thyroid cancer with RAS mutations, initially reported, has been overturned by the recent finding of the cooperative role of TERT mutations. Although some animal models support the carcinogenic role of RAS mutations in the thyroid, evidence that adenomas harboring these mutations evolve in carcinomas is lacking. Their poor specificity and sensitivity make the clinical impact of RAS mutations on the management of thyroid nodules with indeterminate cytology unsatisfactory. Evidence suggests that RAS mutation-positive benign nodules demand a conservative treatment. To have a clinical impact, RAS mutations in thyroid malignancies need not to be considered alone but rather together with other genetic abnormalities in a more general context.


2021 ◽  
Author(s):  
Philippe Lothaire ◽  
Pierrick Uzureau ◽  
Karim Zouaoui Boudjelta ◽  
Nathalie Nagy ◽  
Carine Michiels ◽  
...  

Abstract PurposeUltrasound-guided fine-needle aspiration is the most sensitive investigation procedure in the evaluation of patients with thyroid nodules; however, despite the level of achieved precision, it is still impossible to preoperatively discriminate between follicular adenomas and carcinomas. Thus, no current detection tool of thyroid nodule has both high sensitivity and high positive predictive value for the diagnosis of thyroid cancer. Ultrasound images provide information that are currently missed due to visual interpretation, including the roughness of the echotexture. However, such information can be retrieved using the measurement of the fractal dimension (FD).Material and methodsAccording to the box-counting method, we measured the FD of the echotexture of ultrasound images of 13 benign thyroid nodules and 14 malignant thyroid nodules compared to normal thyroid tissue from 10 men and 16 women (mean age 40).ResultsThe difference of the FD value between malignant nodules (median FD 2.31) and corresponding normal tissues (median FD 2.184) was significant (p<0.001) while the FD values for the benign nodules (median FD 2.21) and for corresponding normal tissues (median FD 2.231) could not be distinguished (p=0.78).ConclusionsThis preliminary work revealed that FD would be an additional feature to discriminate benign from malignant nodules. A larger sampling is now required to confirm the possible utilization of FD in the thyroid cancer diagnosis in clinical practice.


2018 ◽  
Vol 50 (12) ◽  
pp. 922-931 ◽  
Author(s):  
Yuji Nagayama

AbstractThe association between thyroid cancer and thyroid autoimmunity has long been suggested, but remains to be elucidated for several decades. Here the data on this issue are updated by summarizing relevant papers published between 2012 and early 2018. Although numerous papers demonstrated the significant increase in the prevalence of thyroid autoimmunity (positive intrathyroidal lymphocyte infiltration and/or anti-thyroglobulin/thyroid peroxidase antibodies) in patients with thyroid cancers as compared to those with benign nodules, and also the significant increase in the prevalence of papillary thyroid cancer (PTC) in patients with thyroid autoimmunity as compared to those without, there are some crucial biases that should be taken into account for their interpretation. However, a difference in the incidence of thyroid autoimmunity in patients with PTCs and those with other types of thyroid cancers appears to support the significant association of two conditions. Thyroid autoimmunity is, at least partly, likely to be elicited against antigens shared by normal and cancerous thyroid tissues, thereby inducing autoimmunity. At the same time, elevated TSH levels (even within the normal reference ranges), which often accompany Hashimoto’s patients are a risk factor for thyroid cancer. However, it is still unclear whether or not the co-existence of thyroid autoimmunity impacts on cancer characteristics and prognosis. This issue needs to be further investigated with large-scale prospective studies.


Author(s):  
Bita Faam ◽  
Ata A Ghadiri ◽  
Mohammad Ali Ghaffari ◽  
Mehdi Totonchi ◽  
Layasadat Khorsandi

Background: Oxidative stress is commonly accrued in thyroid tissue during hormone synthesis. Objectives: We aimed to examine oxidative stress in patients with thyroid cancer, benign thyroid nodules, and healthy individuals. Methods: In this study, 138 individuals were involved. Among the selected participants, 108 had thyroid nodules, including 30 papillary thyroid cancer (PTC), 30 follicular thyroid cancer (FTC), six anaplastic thyroid cancer (ATC), 12 medullary thyroid cancer (MTC), and 30 benign nodules. In addition, 30 individuals were selected as a healthy control group. The levels of total antioxidant capacity (TAC) and total oxidant status (TOS) of thyroid tissue were measured using the ELISA method, and the oxidative stress index (OSI) was calculated. Results: The TAC level was significantly lower in MTC and FTC subtypes than in controls. The TOS level was considerably higher in the MTC group than in the control and benign nodule groups. The TOS level was not changed in other groups. The OSI was considerably higher in MTC and FTC subtypes. The TAC and OSI in benign nodules were significantly lower and higher than those of controls, respectively. The OSI was higher in female patients than in males. Conclusions: The OSI can not be considered a diagnostic biomarker for benign nodules and MTC. The diverse oxidative stress status between genders may be related to the elevated cancer incidence in females.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A856-A856
Author(s):  
Narudee Churdsuwanrak ◽  
Robert Niihara ◽  
Kristiana Rood ◽  
Celina Yamauchi ◽  
Kharl Wright ◽  
...  

Abstract Fine-needle aspiration (FNA) is one of the most accurate modes of obtaining thyroid nodule biopsies, however, up to 25% of biopsies still yield indeterminate results. There is an increasing number of thyroidectomies due to indeterminate nodules by FNA alone. Therefore, more accurate and time efficient diagnostic approaches for analyzing indeterminate thyroid nodules is required. Recent studies showed that Enigma is associated with different cancer types, including thyroid cancer progression and calcification through its interaction with bone morphogenic protein-1 (BMP-1) and tyrosine kinases linked to mitogen-activated protein kinase (MAPK) signaling pathway. Our published data on Enigma protein analysis with immunohistochemistry showed promising findings to discriminate malignant versus benign nodules. We also showed a thyroid cancer stage-dependent enhancement of Enigma protein expression. In this study, we are investigating Enigma at a gene expression level by quantitative reverse transcription polymerase chain reaction (RT-qPCR), which is more time-efficient, quantitative, and requires less tissue than immunohistochemistry. We extracted mRNA/DNA/proteins from fresh malignant and benign thyroid nodules using a Qiagen AllPrep DNA/RNA/Protein Mini Kit. After verification of the quantity and purity by NanoDrop, isolated mRNA was then run through Enigma-RT-qPCR. MAPK assay was done by western blotting using MAPK-antibody. Our initial results found that Enigma-mRNA expression level was 3-fold higher in malignant compared to benign thyroid tissues. This finding supports our previous protein expression data with a relative quantitative difference in Enigma-mRNA expression level between malignant and benign thyroid nodules. MAPK expression was upregulated in thyroid cancer compared to benign nodules. We conclude that Enigma-RT-qPCR can be used effectively in FNA samples derived from thyroid nodules, which could potentially enhance the diagnostic accuracy of indeterminate nodules and decrease unnecessary thyroidectomies. Furthermore, both Enigma and MAPK were highly expressed in advanced tumor in the same tissues. Future study is needed to establish the functional interaction of Enigma-MAPK activity in thyroid cancer cells.


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