Prevalence and Spectrum of DICER1 Mutations in Adult-onset Thyroid Nodules with Indeterminate Cytology

2021 ◽  
Author(s):  
Anne-Sophie Chong ◽  
Yuri E Nikiforov ◽  
Vincenzo Condello ◽  
Abigail I Wald ◽  
Marina N Nikiforova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
The United States ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Pathogenic Variant ◽  
Driver Mutations ◽  
Adult Onset ◽  
Hotspot Mutations ◽  
Dicer1 Syndrome

Abstract Context DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective Determine (1) the prevalence of DICER1 hotspot mutations in thyroid nodules; (2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; (3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Methods Population-based study of 14 993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot–positive cases, we selected 61, matched to DICER1 hotspot–negative nodules. We performed full sequencing of all exons and exon–intron boundaries of DICER1. Setting Commercial and university-based laboratories in the United States and Canada. Results Among 14 993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot–positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot–negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot–negative nodules (32/61) than in DICER1 hotspot-–positive nodules (4/59) (P < .0001). Conclusion DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer–related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

scholarly journals Prevalence and Spectrum of DICER1Mutations in Adult-Onset Thyroid Nodules

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A868-A869
Author(s):  
Anne-Sophie Chong ◽  
Yuri E Nikiforov ◽  
Vincenzo Condello ◽  
Abigail Wald ◽  
Marina Nikiforova ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
The United States ◽  
Needle Aspiration ◽  
Differentiated Thyroid Carcinoma ◽  
Pathogenic Variant ◽  
Driver Mutations ◽  
Adult Onset ◽  
Hotspot Mutations ◽  
Dicer1 Syndrome

Abstract Context: DICER1 mutations are found in multinodular goiter and differentiated thyroid carcinoma in children, and can be a manifestation of DICER1 syndrome, but the prevalence of DICER1 mutations and their significance in adult-onset thyroid nodules is unknown. Objective: Determine 1) the prevalence of DICER1 hotspot mutations in thyroid nodules; 2) the frequency of a second DICER1 pathogenic variant in thyroid nodules with DICER1 hotspot mutations; 3) the prevalence of other thyroid cancer driver mutations in thyroid nodules with and without DICER1 hotspot mutations. Design: Population-based study of 14,993 consecutive fine needle aspiration biopsies of thyroid nodules evaluated by ThyroSeq v3. From 214 DICER1 hotspot-positive cases, we selected 61, matched to DICER1 hotspot-negative nodules. We performed full sequencing of all exons and exon-intron boundaries of DICER1. Setting: Commercial and university-based laboratories in the United States and Canada Results: Among 14,993 thyroid nodules, 214 (1.4%) revealed a DICER1 hotspot mutation. A second pathogenic/likely pathogenic variant in DICER1 was found in 45/59 (76%) DICER1 hotspot-positive nodules studied while no other DICER1 variant was identified in the DICER1 hotspot-negative group by full DICER1 sequencing. Other alterations in thyroid-related genes were significantly more frequent in DICER1 hotspot-negative nodules (32/61) than in DICER1 hotspot-positive nodules (4/59) (p<0.0001). Conclusions: DICER1 alterations occur in a proportion of adult thyroid nodules and appear mutually exclusive with alterations in other thyroid cancer-related genes. DICER1 hotspot mutations occur with a second hit in most cases and could suggest occult DICER1 syndrome in adults with thyroid nodules.

scholarly journals Diagnostic Strategies for Thyroid Nodules Based on Ultrasonographic Findings in Japan

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4629
Author(s):  
Hiroki Shimura ◽  
Yoshiko Matsumoto ◽  
Tsukasa Murakami ◽  
Nobuhiro Fukunari ◽  
Masafumi Kitaoka ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Diagnostic Criteria ◽  
Thyroid Nodules ◽  
The United States ◽  
Needle Aspiration ◽  
Aspiration Cytology ◽  
Management Guidelines ◽  
Diagnostic Strategies ◽  
Needle Aspiration Cytology ◽  
Meta Analyses

In recent years, the incidence of thyroid cancer has been increasing worldwide, which is believed to be mainly due to the widespread use of imaging examinations, such as ultrasonography. In this context, ultrasonography has become increasingly important because it can evaluate not only the presence or absence of nodules, but also the detailed characteristics of the nodule, making it possible to diagnose benign or malignant nodules before cytology is performed. In Japan, the third edition of the sonographic diagnostic criteria for thyroid nodules is currently widely used, and its content is similar to that of recent meta-analyses and guidelines from medical societies in other countries. In addition, since overdiagnosis of very-low-risk thyroid cancer has recently become an issue, criteria for the implementation of fine needle aspiration cytology (FNAC) have been published by various countries. The Japan Society of Breast and Thyroid Sonology provides guidelines for FNAC implementation for solid and cystic nodules. In the United States, the ATA, NCCA, and ACR have published guidelines, whereas in Europe, the ESMO and ETA have done the same. All of these guidelines used to classify risk are based on nodule size and sonographic findings. This article outlines the diagnostic criteria and management guidelines in Japan in comparison with those published in other countries. Case studies using actual images were also performed to examine the differences in the FNAC guidelines.

Molecular Diagnostics of Thyroid Tumors

2011 ◽  
Vol 135 (5) ◽  
pp. 569-577 ◽  
Author(s):  
Yuri E. Nikiforov
Keyword(s):  
Thyroid Cancer ◽  
Molecular Markers ◽  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Genetic Alterations ◽  
Braf V600e ◽  
Fine Needle ◽  
Molecular Alterations ◽  
Diagnostic Use

Abstract Context.—Thyroid cancer is the most common type of endocrine malignancy and its incidence is steadily increasing. Papillary carcinoma and follicular carcinoma are the most common types of thyroid cancer and represent those tumor types for which use of molecular markers for diagnosis and prognostication is of high clinical significance. Objective.—To review the most common molecular alterations in thyroid cancer and their diagnostic and prognostic utility. Data Sources.—PubMed (US National Library of Medicine)–available review articles, peer-reviewed original articles, and experience of the author. Conclusions.—The most common molecular alterations in thyroid cancer include BRAF and RAS point mutations and RET/PTC and PAX8/PPARγ rearrangements. These nonoverlapping genetic alterations are found in more than 70% of papillary and follicular thyroid carcinomas. These molecular alterations can be detected in surgically resected samples and fine-needle aspiration samples from thyroid nodules and can be of significant diagnostic use. The diagnostic role of BRAF mutations has been studied most extensively, and recent studies also demonstrated a significant diagnostic utility of RAS, RET/PTC, and PAX8/PPARγ mutations, particularly in thyroid fine-needle aspiration samples with indeterminate cytology. In addition to the diagnostic use, BRAF V600E mutation can also be used for tumor prognostication, as this mutation is associated with higher rate of tumor recurrence and tumor-related mortality. The use of these and other emerging molecular markers is expected to improve significantly the accuracy of cancer diagnosis in thyroid nodules and allow more individualized surgical and postsurgical management of patients with thyroid cancer.

Differences of US-FNA BSRTC class, postoperative pathology, and mutation landscape of thyroid nodules between China and other countries.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3055-3055
Author(s):  
Yuntao Song ◽  
Jie Liu ◽  
Weiran Wang ◽  
Tonghui Ma
Keyword(s):  
United States ◽  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Malignant Tumors ◽  
The United States ◽  
Braf V600e ◽  
Class V ◽  
Ras Mutation ◽  
First Choice ◽  
Significant Difference

3055 Background: Ultrasound and ultrasound-guided fine needle aspiration (US-FNA) are the first choice for judging benign and malignant thyroid nodules. This study will report on the differences of US-FNA BSRTC class, postoperative pathology and mutation landscape of thyroid nodules between China and other countries. Methods: We conducted a prospective study containing 383 FNA samples of thyroid nodules. For most of these FNA samples, genomic DNA and RNA were extracted and sequenced with FSZ-Thyroid NGS Panel V1, and postoperative pathology were followed up. Moreover, we also compared results of this study with those of West China Hospital in China, Yamashita Thyroid Hospital in Japan, and Cleveland Clinic in the United States. Results: Among the 383 FNA samples, the proportions of BSRTC class I to VI were 10.7%, 6.3%, 18.8%, 3.7%, 12.3%, and 48.3% respectively. Compared with study in other countries, the proportion of class II was significantly lower than that in Japan and the United States. Meanwhile, the proportion of class V and VI were significantly higher than the above two countries. Subsequently, 232 thyroid nodules were surgically removed. Postoperative pathology showed that the proportion of malignant tumors (85.3%) was also significantly higher than reported in Japan and the United States. But compared with other studies in China, there was no significant difference. Most of the malignant tumors were papillary thyroid cancer (PTC, 96%), accompanied with 2 follicular thyroid cancer (FTC), 3 medullary cancer (MTC) and 3 anaplastic thyroid cancer (ATC). Compared with study in the United States, the proportion of PTC and FTC were elevated (96% vs. 85.3%) and reduced (1% vs. 9.3%) respectively. At last, we also analysis the mutation landscape of 180 malignant tumors. Compared with TCGA study, the frequency of BRAF V600E in PTC in our study was significantly higher than that of TCGA (73.3% vs. 58%), and the frequency of RAS mutation was significantly lower (1.2% vs. 12.6%). And compared with an institutional experience of ThyroSeq v3 for Bethesda III and IV at the University of Pittsburgh Medical Center, the frequency of BRAF V600E and RAS mutation in Bethesda III-IV malignant tumors was also significantly higher (45.8% vs. 1.4%) and lower (8.3% vs. 47.1%). Conclusions: There were significant differences in BSRTC class and postoperative pathology between China and other countries, such as Japan and the United States. The possible reasons included that the indications for FNA in China were different. For example, most of patients who underwent FNA in this study had suspicious clinical/ultrasound features. So the proportion of BSRTC class V and VI as well as the malignant rate were elevated. On the other hand, more BRAF V600E and less RAS mutations were detected in malignant tumors in this study which might result from racial differentiation and discrepancy in proportion of PTC and FTC.

scholarly journals What is New on Thyroid Cancer Biomarkers

2008 ◽  
Vol 3 ◽  
pp. BMI.S669 ◽  
Author(s):  
Rosaria M. Ruggeri ◽  
Alfredo Campennì ◽  
Sergio Baldari ◽  
Francesco Trimarchi ◽  
Maria Trovato
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Follicular Epithelium ◽  
Routine Practice ◽  
Appropriate Treatment ◽  
Follicular Lesions ◽  
Needle Aspiration Cytology ◽  
Well Differentiated

Thyroid cancer harbours in about 5% of thyroid nodules. The majority of them are well-differentiated cancers originating from the follicular epithelium, and are subdivided into papillary and follicular carcinomas. Undifferentiated carcinomas and medullary thyroid carcinomas arising from C cells are less common. Although most thyroid nodules are benign, distinguishing thyroid cancer from benign lesions is crucial for an appropriate treatment and follow-up. The fine needle aspiration cytology (FNAC) allows the diagnosis of nature of thyroid nodules in the majority of cases. However, FNAC has some limitations, particularly in the presence of follicular lesions which can appear dubious in rare instances even at histology. In an effort to improve diagnostic accuracy and offer new prognostic criteria, several immunohistochemical and molecular markers have been proposed. However, most of them have to be validated on large series before being used in routine practice.

NO BENEFIT OF DEDICATED THYROID NODULE SCREENING IN PATIENTS WITH ACROMEGALY

2020 ◽  
Vol 26 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Ngan Betty Lai ◽  
Dave Garg ◽  
Anthony P. Heaney ◽  
Marvin Bergsneider ◽  
Angela M. Leung
Keyword(s):  
United States ◽  
Growth Hormone ◽  
Thyroid Cancer ◽  
Growth Factor ◽  
Thyroid Nodule ◽  
Fine Needle Aspiration ◽  
Thyroid Nodules ◽  
Needle Aspiration ◽  
Papillary Thyroid ◽  
Fine Needle

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.). Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology. Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed). Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly. Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States

Intraoperative Frozen Section Performance for Thyroid Cancer Diagnosis

2021 ◽  
Author(s):  
Iuri Martin Goemann ◽  
Francisco Paixão ◽  
Alceu Migliavaca ◽  
José Ricardo Guimarães ◽  
Rafael Selbach Scheffel ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Diagnosis ◽  
Thyroid Nodules ◽  
Frozen Section ◽  
Needle Aspiration ◽  
Intraoperative Frozen Section ◽  
Indeterminate Nodules ◽  
Intraoperative Management ◽  
Low Sensitivity ◽  
Sensitivity Specificity

Abstract Purpose: A primary medical relevance of thyroid nodules consists of excluding thyroid cancer, present in approximately 5% of all thyroid nodules. Fine-needle aspiration biopsy (FNAB) has a paramount role in distinguishing benign from malignant thyroid nodules due to its availability and diagnostic performance. Nevertheless, intraoperative frozen section (iFS) is still advocated as a valuable tool for surgery planning, especially for indeterminate nodules. Methods: To compare the FNAB and iFS performances in thyroid cancer diagnosis among nodules in Bethesda Categories (BC) I to VI. The performance of FNAB and iFS tests were calculated using final histopathology results as the gold standard.Results: In total, 316 patients were included in the analysis. Both FNAB and iFS data were available for 272 patients (86.1%). The overall malignancy rate was 30.4%% (n=96). The FNAB sensitivity, specificity, and accuracy for benign (BC II) and malignant (BC V and VI) were 89.5%, 97.1%, and 94.1%, respectively. For all nodules evaluated, the iFS sensitivity, specificity, and accuracy were 80.9%, 100%, and 94.9%, respectively. For indeterminate nodules and follicular lesions (BC III and IV), the iFS sensitivity, specificity, and accuracy were 25%, 100%, and 88.7%, respectively. For BC I nodules, iFS had 95.2% of accuracy.Conclusion: Our results do not support routine iFS for indeterminate nodules or follicular neoplasms (BC III and IV) due to its low sensitivity. In these categories, iFS is not sufficiently accurate to guide the intraoperative management of thyroidectomies. iFS for BC I nodules could be a reasonable option and should be specifically investigated.

scholarly journals Adrenal metastasis as the initial diagnosis of synchronous papillary and follicular thyroid cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Xin He ◽  
Scott A. Soleimanpour ◽  
Gregory A. Clines
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodules ◽  
Follicular Thyroid Carcinoma ◽  
Distant Metastases ◽  
Needle Aspiration ◽  
Left Lobe ◽  
Adrenal Metastasis ◽  
Bethesda Classification ◽  
The Right

Abstract Background Differentiated thyroid cancer uncommonly presents with distant metastases. Adrenal metastasis from differentiated thyroid cancer presenting as the initial finding is even less common. Case Presentation A 71-year-old male was incidentally found on chest CT to have bilateral thyroid nodules, which were confirmed on ultrasound. Fine needle aspiration of the dominant right 3.3 cm nodule contained histologic features most consistent with Bethesda classification III, and repeat fine needle aspiration revealed pathology consistent with Bethesda classification II. Follow-up thyroid ultrasound showed 1% increase and 14% increase in nodule volume at one and two years, respectively, compared to baseline. Prior to the second annual thyroid ultrasound, the patient was incidentally found to have a 4.1 cm heterogeneously enhancing mass in the right adrenal gland on CT of the abdomen and pelvis. Biochemical evaluation was unremarkable with the exception of morning cortisol of 3.2 µg/dL after dexamethasone suppression. The patient then underwent laparoscopic right adrenal gland excision, which revealed metastatic follicular thyroid carcinoma. Total thyroidectomy was then performed, with pathology showing a 4.8 cm well-differentiated follicular thyroid carcinoma of the right lobe, a 0.5 cm noninvasive follicular thyroid neoplasm with papillary-like nuclear features of the left lobe, and a 0.1 cm papillary microcarcinoma of the left lobe. Thyrotropin-stimulated whole body scan showed normal physiologic uptake of the remnant thyroid tissue without evidence of other iodine avid disease. The patient then received radioactive iodine. At follow-up 14 months after total thyroidectomy, he remains free of recurrent disease. Conclusion Despite following the recommended protocol for evaluation and surveillance of thyroid nodules, thyroid cancer can be challenging to diagnose, and may not be diagnosed until distant metastases are identified.

THE RISK OF THYROID CANCER IN PATIENTS WITH THYROID NODULE 3 CM OR LARGER

2020 ◽  
Vol 26 (11) ◽  
pp. 1286-1290
Author(s):  
Edy Kornelius ◽  
Shih-Chang Lo ◽  
Chien-Ning Huang ◽  
Yi-Sun Yang
Keyword(s):  
Thyroid Cancer ◽  
Positive Predictive Value ◽  
Thyroid Carcinoma ◽  
Thyroid Nodule ◽  
Fine Needle Aspiration ◽  
Predictive Value ◽  
Thyroid Nodules ◽  
Fine Needle Aspiration Biopsy ◽  
Needle Aspiration ◽  
Fine Needle

Objective: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger. Methods: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined. Results: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent. Conclusion: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk. Abbreviations: ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; mPTC = micropapillary thyroid carcinoma; NPV = negative predictive value; PPV = positive predictive value; PTC = papillary thyroid carcinoma

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