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.

scholarly journals Telomere-related Genomic Instability in Papillary Thyroid Cancers: A Preliminary Study

2020 ◽  
Author(s):  
Aline Rangel-Pozzo ◽  
Tinuccia Dettori ◽  
Daniela Virginia Frau ◽  
John Gartner ◽  
Garbor Fisher ◽  
...  
Keyword(s):  
Telomere Length ◽  
Genomic Instability ◽  
Genome Instability ◽  
Papillary Thyroid ◽  
Benign Lesions ◽  
Follicular Variant ◽  
Correct Treatment ◽  
Follicular Thyroid Adenoma ◽  
Preliminary Study ◽  
Selection Of

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 3D nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 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). NIFTP has longer telomeres than CL-PTC and FV-PTC samples and telomere length overlaps in NIFTP and FTA. There was no association between BRAF expression and telomere length in all tested samples. Our data showing that 3D nuclear telomere organization is altered differently in thyroid cancer variants, suggest that this parameter might guide clinical management of NIFTP. Although further investigations in a larger cohort of patients are necessary to corroborate our observations, telomere-related genomic instability might be of value in the diagnosis of NIFTP and allow for a more appropriate selection of the correct treatment.

scholarly journals Controversies Regarding the Interpretation of Follicular Thyroid Nodules

2019 ◽  
Vol 143 (12) ◽  
pp. 1472-1476 ◽  
Author(s):  
Saul Suster
Keyword(s):  
Personal Experience ◽  
Thyroid Nodules ◽  
Follicular Carcinoma ◽  
Malignant Neoplasms ◽  
Common Source ◽  
Low Grade ◽  
Review Of The Literature ◽  
Benign Lesions ◽  
Follicular Variant ◽  
Diagnostic Difficulties

Context.— Follicular nodules are the most common source of diagnostic difficulties in the practice of surgical pathology of the thyroid. This is due to a variety of factors, the most salient of which is the lack of well-defined criteria and evidence-based data for the diagnosis of these lesions. Objectives.— To discuss some of the assumptions that have been accrued over the years regarding the criteria by which we evaluate such lesions. Data Sources.— The information presented herein is based on review of the literature and the author's personal experience. Conclusions.— Thyroid nodules with a predominant follicular growth pattern span the range from benign lesions (hyperplastic nodules, adenomatoid nodules, follicular adenomas) to malignant neoplasms (follicular carcinoma, follicular variant of papillary carcinoma) with a host of intermediate or indeterminate lesions found in between. Advances in immunohistochemistry and molecular pathology have not yet provided a reliable way of separating the borderline or intermediate cases. Low-grade and intermediate or borderline follicular-patterned thyroid lesions are those most often prone to difficulties for interpretation. Newer and potential future approaches for the evaluation of these lesions are discussed.

scholarly journals Diffuse Follicular Variant of Papillary Thyroid Carcinoma: A Case Report with a Revision of Literature

Rare Tumors ◽  
2016 ◽  
Vol 8 (4) ◽  
pp. 159-161 ◽  
Author(s):  
Gian Luca Rampioni Vinciguerra ◽  
Niccolò Noccioli ◽  
Armando Bartolazzi
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Young Women ◽  
Unusual Case ◽  
Thyroid Nodules ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Few Data ◽  
Thyroid Parenchyma ◽  
Nuclear Features

The diffuse follicular variant of papillary thyroid carcinoma (DFV-PTC) is a rare malignant thyroid condition. It represents an uncommon variant of papillary carcinoma characterized by a diffuse involvement of thyroid parenchyma, follicular architecture and nuclear features of PTC in absence of a surrounding capsule. Up to date few data have been collected about this entity and, at the best of our knowledge, only 24 cases have been reported in the literature. According to these reports DFV-PTC seems to occur preferentially in young women and shows more aggressive behavior than other papillary thyroid tumors. Herein we present an unusual case of DFV-PTC occurring in an 83 years old woman, involving the entire thyroid gland, without distinct or prevalent thyroid nodules. The tumor was clinically misdiagnosed as obstructive goiter.

scholarly journals Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Tae Sook Hwang ◽  
Wook Youn Kim ◽  
Hye Seung Han ◽  
So Dug Lim ◽  
Wan-Seop Kim ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Mutational Analysis ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Ras Mutation ◽  
Ras Mutations ◽  
Codon 61

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n=57), BRAF K601E (n=11), or RAS (n=64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

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.

Fine Needle Aspiration Analysis of B-RAF in Thyroid Nodules

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P37-P38
Author(s):  
Brandon G Bentz ◽  
Brian Thomas Miller ◽  
Joseph Holden ◽  
Leslie R Rowe ◽  
Joel Bentz
Keyword(s):  
Fine Needle Aspiration ◽  
Braf Mutation ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Biological Behavior ◽  
Melting Curve Analysis ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Fine Needle ◽  
Mutational Status

Objective Fine needle aspiration (FNA) represents the most useful initial diagnostic tool with which to analyze thyroid nodules for carcinoma. A mutation of the B-type RAF kinase (BRAF) represents the most common genetic alteration in sporadic papillary thyroid cancer (PTC), and may signify a more aggressive biological behavior within PTCs. Our objective was to determine if BRAF analysis of FNA cytology may provide clinically useful information in the analysis of thyroid nodules. Methods An IRB-approved retrospective chart review of clinically relevant data for classic PTCs (CPTC), follicular-variant of PTC (FV-PTC), or non-malignant goiter was performed following a blinded pathologic re-review. Both pathologic and cytology samples were analyzed by fluorescent melting curve analysis (FMCA) for the V600E mutation of BRAF, and mutational status was compared with clinical information. Results A 100% concordance was found for BRAF mutation determination between the cytologic and final pathologic malignant and benign tissue samples studied. BRAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular-variant of papillary thyroid carcinomas (55.6% vs. 14.3%, p=0.05), and correlated with cytologic interpretation (p=0.025) and histologic diagnosis (p=0.03). Conclusions FMCA of thyroid nodule FNAs can accurately determine the mutational status of the BRAF gene. Since the presence of BRAF mutation can predict a more aggressive biological behavior, an analysis of BRAF mutational status of initial FNAs may add useful information to the list of risk stratification criteria for PTCs.

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