Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Thyroid ◽  
2021 ◽  
Author(s):  
James J Figge ◽  
William E. Gooding ◽  
David L Steward ◽  
Linwah Yip ◽  
Rebecca S Sippel ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Molecular Testing ◽  
Clinical Parameters ◽  
Indeterminate Cytology

scholarly journals MON-LB79 Do Ultrasound Patterns and Clinical Parameters Modify the Probability of Thyroid Cancer Predicted by Molecular Testing in Thyroid Nodules With Indeterminate Cytology?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
James J Figge ◽  
William E Gooding ◽  
Kenneth D Burman ◽  
Sarah Mayson ◽  
Randall P Scheri ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Predictive Ability ◽  
Molecular Testing ◽  
Positive Trend ◽  
American Thyroid Association ◽  
Clinical Parameters ◽  
Increased Risk ◽  
Indeterminate Cytology ◽  
Risk Of Cancer

Abstract Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further modify the risk of cancer in nodules predicted to be positive or negative by molecular testing remains unknown. Aim: To test if clinical parameters, including age, gender, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] system vs American College of Radiology TIRADS), radiation exposure, and family history of thyroid cancer (TC) can modify the probability of TC or NIFTP predicted by MT in thyroid nodules with indeterminate cytology. Methods: We studied 257 thyroid nodules from 10 study centers with fine-needle aspiration (FNA) yielding indeterminate cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression were used for data analysis. Results: In this group of thyroid nodules, out of all parameters studied using univariate regression, patient gender, age, and Bethesda category were significantly associated with TC/NIFTP probability (P<0.05 for each). The ATA US patterns showed a positive trend (P=0.1211), whereas TIRADS was not predictive (P=0.3135). A multivariate regression model incorporating the four most informative covariates (gender, age, Bethesda category, and ATA US patterns) (model #1) yielded a C index=0.653; R2=0.108. Male gender and Bethesda category V significantly increased risk, and age demonstrated a nonlinear risk profile. When TSv3 was added to model #1, the C index increased to 0.888; R2=0.572. However, age (P=0.341), Bethesda category (P=0.272), and the ATA US patterns (P=0.264) had limited predictive ability in comparison with TSv3, which dominated the predictive performance (P<0.001). Gender was the only parameter showing tendency for significance beyond MT (P=0.095). The most parsimonious model incorporated gender and TSv3 (C index=0.889; R2=0.588). Conclusions: While often useful in selecting thyroid nodules for FNA, neither the ATA US nor the TIRADS scoring systems were informative in further predicting TC/NIFTP in thyroid nodules with indeterminate FNA cytology. Although age and Bethesda category were associated with TC/NIFTP probability on univariate analysis, they had limited incremental value above the high predictive ability of TSv3. Gender was the only parameter with potential contribution to predicting TC/NIFTP in addition to MT.

Validation and Multicenter Clinical Experience of the Afirma® Gene Expression Classifier

2014 ◽  
Vol 10 (02) ◽  
pp. 117 ◽  
Author(s):  
Trevor E Angell ◽  
Erik K Alexander ◽  
◽  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Clinical Experience ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Current Data ◽  
Molecular Testing ◽  
Gene Expression Classifier ◽  
Indeterminate Cytology

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.

scholarly journals Highly Sensitive and Specific Molecular Test for Mutations in the Diagnosis of Thyroid Nodules: A Prospective Study of BRAF-Prevalent Population

2020 ◽  
Vol 21 (16) ◽  
pp. 5629 ◽  
Author(s):  
Yoon Young Cho ◽  
So Young Park ◽  
Jung Hee Shin ◽  
Young Lyun Oh ◽  
Jun-Ho Choe ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Prospective Study ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Molecular Testing ◽  
Molecular Test ◽  
Indeterminate Cytology ◽  
A Prospective Study

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70–80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

scholarly journals Validation and Multicenter Clinical Experience of the Afirma® Gene Expression Classifier

2015 ◽  
Vol 11 (1) ◽  
pp. 117
Author(s):  
Trevor E Angell ◽  
Erik K Alexander ◽  
◽  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Clinical Experience ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Current Data ◽  
Molecular Testing ◽  
Gene Expression Classifier ◽  
Indeterminate Cytology

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.

Contemporary Management of Thyroid Nodules

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Kristen Kobaly ◽  
Caroline S. Kim ◽  
Susan J. Mandel
Keyword(s):  
Thyroid Nodules ◽  
Cervical Lymphadenopathy ◽  
Standard Technique ◽  
Clinical History ◽  
Needle Aspiration ◽  
Annual Review ◽  
Publication Date ◽  
Molecular Testing ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Thayse Lozovoy Madsen Barbosa ◽  
Cleo Otaviano Mesa Junior ◽  
Hans Graf ◽  
Teresa Cavalvanti ◽  
Marcus Adriano Trippia ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Needle Aspiration ◽  
Molecular Testing ◽  
American Thyroid Association ◽  
Institutional Review ◽  
The Us ◽  
Risk Of Malignancy ◽  
Indeterminate Cytology

Abstract Background Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. Methods The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. Results Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). Conclusions Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

scholarly journals Papillary Thyroid Carcinoma With Cystic Changes in a Patient With Prior History of Toxic Nodule

2020 ◽  
Vol 8 ◽  
pp. 232470962094267
Author(s):  
Gliceida Maria Galarza Fortuna ◽  
Paola Rios ◽  
Ailyn Rivero ◽  
Gabriela Zuniga ◽  
Kathrin Dvir ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Thyroid Nodule ◽  
Thyroid Nodules ◽  
Molecular Testing ◽  
Papillary Thyroid ◽  
Thyroid Lobectomy ◽  
Cystic Changes ◽  
History Of

Thyroid nodules are palpable on up to 7% of asymptomatic patients. Cancer is present in 8% to 16% of those patients with previously identified thyroid nodules. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for approximately 85% of thyroid cancers. Although most appear as solid nodules on ultrasound imaging, a subset of 2.5% to 6% has cystic components. The presence of cystic changes within thyroid nodules decreases the accuracy of fine needle aspiration (FNA) in the diagnosis of thyroid cancer, given the difficulty of obtaining appropriate cellular content. This becomes a diagnostic and therapeutic challenge. We present a case of a 31-year-old female with a 1-month history of palpitations, fatigue, and night sweats, who underwent evaluation, and was diagnosed with subclinical hyperthyroidism. She presented 4 years later with compressive symptoms leading to repeat FNA, showing Bethesda III-atypia of undetermined significance and negative molecular testing. Thyroid lobectomy revealed PTC with cystic changes. This case is a reminder that patients with hyperfunctioning thyroid nodule should have closer follow-up. It poses the diagnostic dilemma of how much is good enough in the evaluation and management of a thyroid nodule. Early detection and action should be the standard of care.

scholarly journals Evaluation of the PAX8/PPARG Translocation in Follicular Thyroid Cancer with a 4-Color Reverse-Transcription PCR Assay and Automated High-Resolution Fragment Analysis

2010 ◽  
Vol 56 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Alicia Algeciras-Schimnich ◽  
Dragana Milosevic ◽  
Bryan McIver ◽  
Heather Flynn ◽  
Honey V Reddi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
High Resolution ◽  
Reverse Transcription ◽  
Thyroid Tissue ◽  
Molecular Testing ◽  
Analytical Sensitivity ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Fragment Analysis ◽  
Reverse Transcription Pcr

Abstract Background: Molecular testing of thyroid malignancies, in combination with cytologic and histologic examination, is becoming increasingly attractive as a tool for refining traditional morphologic diagnosis. The molecular changes associated with follicular thyroid carcinoma (FTC) are point mutations in RAS oncogenes or the presence of PAX8/PPARG (paired box 8/peroxisome proliferator-activated receptor gamma) rearrangement. Methods: We developed and validated a clinical assay for the detection of PAX8/PPARG rearrangements that uses a 4-color reverse-transcription PCR (RT-PCR) assay and high-resolution fragment analysis. Results: The RT-PCR assay is applicable for detecting the various described fusion transcripts of PAX8/PPARG in formalin-fixed, paraffin-embedded thyroid tissue and in fine-needle aspirate biopsy washes from thyroid nodules. The analytical sensitivity of the assay is 1 abnormal cell in a background of 100–10 000 translocation-negative cells. A comparison of the RT-PCR assay with dual-fusion fluorescence in situ hybridization showed an overall concordance of 95%. With this assay, we obtained a prevalence for the PAX8/PPARG rearrangement in FTC of 62% (13 of 21 cases), compared with a 5% prevalence (3 of 55) for other follicular cell–derived neoplasms. Conclusions: The introduction of this assay into clinical practice could provide useful information for the diagnosis and possibly for the prognosis and treatment of thyroid cancer in the future.

Sign in / Sign up

Export Citation Format

Share Document