Raman Spectroscopy Discloses Altered Molecular Profile in Thyroid Adenomas

Follicular patterned nodules are sometimes complex to be classified due to ambiguous nuclear features and/or questionable capsular or vascular invasion. In this setting, there is a poor inter-observer concordance even among expert pathologists. Raman spectroscopy was recently used to separate benign and malignant thyroid nodules based on their molecular fingerprint; anyway, some histologically proved follicular adenomas were clustered as having a characteristic profile of malignant lesions. In this study, we analyzed five follicular thyroid adenomas with a malignant spectroscopic profile compared to five follicular adenomas with a benign Raman spectrum in order to assess possible molecular differences between the two groups. Morphological, immunohistochemical, and molecular analyses evidenced expression of malignancy-associated proteins in four out of five malignant clustered adenomas. The remaining malignant clustered adenoma showed a TSHR mutation previously associated with autonomously functioning follicular carcinomas. In conclusion, thyroid follicular adenomas are a group of morphologically benign neoplasms that may have altered the mutational or expression profile; cases of adenomas with altered immunophenotype are recognized as showing a profile associated with malignancy by Raman spectroscopy. This correlation warrants a more extensive evaluation and suggests a potential predictive value of spectroscopic assessment in recognizing characteristics associated with tumor progression in follicular thyroid neoplasms.

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Thyroid Adenomas in Children

Annals of the Russian academy of medical sciences ◽

10.15690/vramn.v70.i5.1436 ◽

2015 ◽

Vol 70 (5) ◽

pp. 513-518

Author(s):

D. A. Morozov ◽

E. S. Pimenova ◽

E. D. Mirokova

Keyword(s):

Thyroid Gland ◽

Thyroid Nodules ◽

Clinical Symptoms ◽

Nodular Goiter ◽

Surgical Approaches ◽

Number Of Patients ◽

Thyroid Adenomas ◽

Malignant Lesions ◽

Treatment Prognosis ◽

Cancer In Children

According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years.

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Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center

Cancers ◽

10.3390/cancers14020420 ◽

2022 ◽

Vol 14 (2) ◽

pp. 420

Author(s):

Paola Vignali ◽

Agnese Proietti ◽

Elisabetta Macerola ◽

Anello Marcello Poma ◽

Liborio Torregrossa ◽

...

Keyword(s):

Retrospective Cohort ◽

Thyroid Neoplasms ◽

Molecular Profile ◽

Follicular Neoplasm ◽

Cytological Diagnosis ◽

Careful Monitoring ◽

Non Invasive ◽

Indeterminate Cytology ◽

Nuclear Features ◽

Molecular Evaluation

Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

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The Accuracy of ACR TI-RADS Classification of Neck Ultrasound as a First-Line Diagnostic Approach for Thyroid Neoplasms in Pediatric Patients: A Retrospective Study

Oncopediatrics ◽

10.15690/onco.v5i1.1862 ◽

2018 ◽

Vol 5 (1) ◽

pp. 13-23

Author(s):

Nikolai S. Grachev ◽

Elena V. Feoktistova ◽

Igor N. Vorozhtsov ◽

Natalia V. Babaskina ◽

Ekaterina Yu. Iaremenko ◽

...

Keyword(s):

Thyroid Cancer ◽

Predictive Value ◽

Thyroid Nodules ◽

Pediatric Patients ◽

Thyroid Neoplasms ◽

Diagnostic Methods ◽

Diagnostic Approach ◽

First Line ◽

Neck Ultrasound

Background.Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. However, in some instances limitations and shortcomings arise, making it insufficient for determining a specific diagnosis.Objective.Our aim was to evaluate the effectiveness of ACR TI-RADS classification of neck ultrasound as a first-line diagnostic approach for thyroid neoplasms in pediatric patients.Methods.A retrospective analysis was made of FNA and US protocols in 70 patients who underwent the examination and treatment at Dmitry Rogachev National Research Center between January 2012 and August 2017. In the retrospective series 70% (49/70) of patients undergone FNA and 43% (30/70) of them undergone repeated FNA. All US protocols were interpreted according to ACR TI-RADS system by the two independent experts. The clinical judgment was assessed using the concordance test and the reliability of preoperative diagnostic methods was analized.Results.According to histologic examination protocols, benign nodules reported greater multimorbidity 29% (20/70), compared with thyroid cancer 17% (12/70), complicating FNA procedure. A statistically significant predictor of thyroid cancer with a tumor size ACR TI-RADS showed a significant advantage of ACR TI-RADS due to higher sensitivity (97.6 vs 60%), specificity (78.6 vs 53.8%), positive predictive value (87.2 vs 71.4%), and negative predictive value (95.7 vs 41.2%). Concordance on the interpreted US protocols according to ACR TI-RADS classification between two experts was high, excluding accidental coincidence.Conclusion.The data support the feasibility of US corresponding to the ACR TI-RADS classification as a first-line diagnostic approach for thyroid neoplasm reducing the number of unnecessary biopsies for thyroid nodules.

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Rate of non-invasive follicular thyroid neoplasms with papillary-like nuclear features depends on pathologist’s criteria: a multicentre retrospective Southern European study with prolonged follow-up

Endocrine ◽

10.1007/s12020-021-02610-7 ◽

2021 ◽

Author(s):

Miguel Paja ◽

Carles Zafón ◽

Carmela Iglesias ◽

Aitziber Ugalde ◽

Jose Manuel Cameselle-Teijeiro ◽

...

Keyword(s):

Thyroid Neoplasms ◽

European Study ◽

Non Invasive ◽

Nuclear Features

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Optical Biomarkers for the Diagnosis of Osteoarthritis through Raman Spectroscopy: Radiological and Biochemical Validation Using Ex Vivo Human Cartilage Samples

Diagnostics ◽

10.3390/diagnostics11030546 ◽

2021 ◽

Vol 11 (3) ◽

pp. 546

Author(s):

Paula Casal-Beiroa ◽

Vanesa Balboa-Barreiro ◽

Natividad Oreiro ◽

Sonia Pértega-Díaz ◽

Francisco J. Blanco ◽

...

Keyword(s):

Raman Spectroscopy ◽

Articular Cartilage ◽

Ex Vivo ◽

Cartilage Degradation ◽

Calcium Pyrophosphate ◽

Calcium Pyrophosphate Dihydrate ◽

Label Free ◽

Molecular Fingerprint ◽

Human Cartilage ◽

Biochemical Validation

Osteoarthritis (OA) is the most common rheumatic disease, characterized by progressive articular cartilage degradation. Raman spectroscopy (RS) has been recently proposed as a label-free tool to detect molecular changes in musculoskeletal tissues. We used cartilage samples derived from human femoral heads to perform an ex vivo study of different Raman signals and ratios, related to major and minor molecular components of articular cartilage, hereby proposed as candidate optical biomarkers for OA. Validation was performed against the radiological Kellgren–Lawrence (K-L) grading system, as a gold standard, and cross-validated against sulfated glycosaminoglycans (sGAGs) and total collagens (Hyp) biochemical contents. Our results showed a significant decrease in sGAGs (SGAGs, A1063 cm−1/A1004 cm−1) and proteoglycans (PGs, A1375 cm−1/A1004 cm−1) and a significant increase in collagen disorganization (ColD/F, A1245 cm−1/A1270 cm−1), with OA severity. These were correlated with sGAGs or Hyp contents, respectively. Moreover, the SGAGs/HA ratio (A1063 cm−1/A960 cm−1), representing a functional matrix, rich in proteoglycans, to a mineralized matrix-hydroxyapatite (HA), was significantly lower in OA cartilage (K-L I vs. III–IV, p < 0.05), whilst the mineralized to collagenous matrix ratio (HA/Col, A960 cm−1/A920 cm−1) increased, being correlated with K-L. OA samples showed signs of tissue mineralization, supported by the presence of calcium crystals-related signals, such as phosphate, carbonate, and calcium pyrophosphate dihydrate (MGP, A960 cm−1/A1004 cm−1, MGC, A1070 cm−1/A1004 cm−1 and A1050 cm−1/A1004 cm−1). Finally, we observed an increase in lipids ratio (IL, A1450 cm−1/A1670 cm−1) with OA severity. As a conclusion, we have described the molecular fingerprint of hip cartilage, validating a panel of optical biomarkers and the potential of RS as a complementary diagnostic tool for OA.

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Risk of Malignancy in Thyroid Nodules Using the American College of Radiology Thyroid Imaging Reporting and Data System in the NIFTP Era

Hormone and Metabolic Research ◽

10.1055/a-0743-7326 ◽

2018 ◽

Vol 50 (10) ◽

pp. 735-737 ◽

Cited By ~ 7

Author(s):

Pedro Rosario ◽

Alexandre da Silva ◽

Maurício Nunes ◽

Michelle Borges

Keyword(s):

Thyroid Nodules ◽

Data System ◽

Thyroid Neoplasm ◽

Malignant Tumours ◽

Thyroid Imaging ◽

Risk Of Malignancy ◽

Nuclear Features

AbstractRecently, the American College of Radiology (ACR) proposed a Thyroid Imaging Reporting and Data System (TI-RADS) for thyroid nodules based on ultrasonographic features. It is important to validate this classification in different centres. The present study evaluated the risk of malignancy in solid nodules>1 cm using ACR TI-RADS. The risk of malignancy was defined including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and after its exclusion from malignant tumours. For the present study, the original images were revised, and each nodule was assigned to one of the TI-RADS levels proposed for solid nodules: TR3, TR4, or TR5. This risk of malignancy was significantly different for the three levels: 1.7%, 11.2%, and 60.6% for TR3, TR4, and TR5, respectively, when NIFTP was included, and 0.6%, 7.9%, and 60.2% for TR3, TR4, and TR5, respectively, when NIFTP was excluded from malignant tumours. The nodules corresponding to NIFTP were classified according to ACR as TR3 in 28.5% of cases, TR4 in 67.8%, and TR5 in only 3.5%. The nodules corresponding to cancer were classified according to ACR as TR3 in only 2.3% of cases, TR4 in 27%, and TR5 in 70.5%. In conclusion, this study shows the validity of the ACR TI-RADS for solid thyroid nodules, even after the exclusion of NIFTP from malignant tumours.

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Diagnostic Value of CK19, HBME-1 and TROP2 Biomarkers in Identification of Different Types of Thyroid Follicular Neoplasms

ACTA MEDICA IRANICA ◽

10.18502/acta.v59i1.5397 ◽

2021 ◽

Author(s):

Shohreh Vojuhi ◽

Masoud Mohebbi ◽

Zohreh Mousavi ◽

Mohammadali Yaghoubi ◽

Reza Ziaolhagh

Keyword(s):

Positive Predictive Value ◽

Papillary Carcinoma ◽

Predictive Value ◽

Thyroid Nodules ◽

Follicular Adenoma ◽

Thyroid Neoplasms ◽

Diagnostic Value ◽

Cross Sectional ◽

Predictive Values ◽

Different Types

Thyroid malignancies are found in 7% to 15% of all thyroid nodules. Immunohistochemical markers, including CK19, HBME-1and TROP2, have shown an effective role in identifying these malignancies. Hence, due to the lack of appropriate diagnostic tests for the identification of thyroid neoplasms, in this study, we aimed to determine the diagnostic value of these biomarkers in the identification of different types of follicular thyroid neoplasms. In this cross-sectional study, paraffin-embedded tissue blocks from the surgical resection of patients with thyroid nodules, referring to Imam Reza and Razavi Hospitals of Mashhad in 2017, were studied. Sensitivity, specificity, and positive and negative predictive values of these biomarkers for the identification of different types of follicular thyroid neoplasms were also studied. 129 patients with a mean age of 44.65±12.59 years participated in this study, of whom 101 (78.29%) were women. The most common type of follicular thyroid neoplasm was papillary carcinoma (60.47%). The highest sensitivity (94.87%) and positive predictive value (68.51%) in the detection of follicular neoplasms was observed by CK19 in papillary carcinoma. The sensitivity and positive predictive value of TROP2 in the detection of papillary neoplasms was 93.58% and 75.25%, respectively. In addition, HBME-1 had the highest specificity (72.54 %) and positive predictive value (81.57%) in identifying this neoplasm. The results of this study showed that CK19, HBME-1, and TROP2 had high diagnostic value in the detection of papillary thyroid neoplasms. Although these biomarkers had low diagnostic value in identifying follicular adenoma and carcinoma, given the high negative predictive value, they can be considered as powerful markers in identifying negative cases.

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Role of biomarkers in predicting the occurrence of thyroid neoplasms in radiation-exposed children

Endocrine Related Cancer ◽

10.1530/erc-17-0408 ◽

2018 ◽

Vol 25 (4) ◽

pp. 481-491

Author(s):

Joseph M Shulan ◽

Leonid Vydro ◽

Arthur B Schneider ◽

Dan V Mihailescu

Keyword(s):

Thyroid Cancer ◽

Thyroid Nodules ◽

Subsequent Development ◽

Thyroid Neoplasms ◽

Childhood Cancer Survivors ◽

Malignant Neoplasms ◽

Increased Risk ◽

Need To Evaluate

With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid nodules and cancer in a cohort of radiation-exposed children. 764 subjects who were irradiated in the neck area as children were examined and followed for up to 25 years. All subjects underwent a clinical examination, measurements of thyrotropin, thyroglobulin levels and thyroid imaging. At baseline, 216 subjects had thyroid nodules and 548 did not. Of those with nodules, 176 underwent surgery with 55 confirmed thyroid cancers. During the follow-up, 147 subjects developed thyroid nodules including 22 with thyroid cancer. Thyroglobulin levels were higher in subjects with prevalent thyroid nodules (26.1 ng/mL vs 9.37 ng/mL; P < 0.001) and in those who had an initial normal examination but later developed thyroid nodules (11.2 ng/mL vs 8.87 ng/mL; P = 0.017). There was no relationship between baseline thyrotropin levels and the prevalent presence or absence of thyroid nodules, whether a prevalent neoplasm was benign or malignant, subsequent development of thyroid nodules during follow-up or whether an incident nodule was benign or malignant. In conclusion, in radiation-exposed children, higher thyroglobulin levels indicated an increased risk of developing thyroid nodules but did not differentiate between benign and malignant neoplasms. There was no association between the baseline TSH level and the risk of developing thyroid nodules or cancer.

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